Contact Lens & Anterior Eye
Volume 31, Issue 4 , Pages 179-187, August 2008

Albumin adsorption to contact lens materials: A review

Centre for Contact Lens Research, School of Optometry, University of Waterloo, 200, University Avenue West, Waterloo, Ontario, N2L 3G1, Canada

published online 07 July 2008.

Article Outline

Abstract 

During contact lens wear, tear film components such as lipids, mucins and proteins tend to deposit on and within the lens material and may cause discomfort, reduced vision and inflammatory reactions. The tear film protein that has attracted most interest when studying contact lens deposition is the small (14kDa), positively charged protein lysozyme. Albumin, which is a much larger protein (66kDa) with an overall net negative charge is also of interest, and shows very different adsorption patterns to lysozyme.

The concentration of albumin in the tear film is relatively low compared to the concentration in blood serum, but this value increases markedly under various conditions, including when the eye is closed, during contact lens wear and in various dry eye states.

Gaining an understanding of the manner in which albumin deposits on biomaterials is of importance for contact lens wear, as well as for other medical applications where HEMA-based materials are used for implants, artificial blood vessels or drug delivery devices.

This review paper summarizes the impact of individual material compositions, water content, hydrophobicity and electrostatic attraction on the adsorption behavior of the protein albumin.

Keywords: Serum albumin, Contact lens materials, Protein deposition

 

Contact lens deposition with substances from the human tear film has been extensively studied [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30]. The majority of published studies have reported on the in vivo or in vitro deposition of either “total protein” [23], [31], [32] or, more specifically, lysozyme [11], [33], [34]. However, lysozyme only accounts for a proportion of the proteins in the tears, with other major tear film proteins such as lactoferrin, albumin and lipocalin being also present in high quantities [35], [36], [37], [38], [39], [40], [41], [42], [43]. To-date, little has been published on the interaction between contact lenses and albumin and the purpose of this review article is to describe the factors that influence the degree to which this protein interacts with various materials used for contact lenses.

Albumin is synthesized in the liver and has an estimated lifetime of 27 days [44], [45]. It is the most abundant protein in human serum and is also the most prominent soluble protein in the body of all vertebrates [44]. Hippocrates (circa 460–370 BC) was probably the first scientist to mention some distinctive properties of albumin in the human body. Serum albumin keeps the osmotic blood pressure and blood pH value constant and transports various molecules, including hormones, fatty acids and drugs [46]. In a human body weighing 70kg, 41% of the total extravascular albumin is found in the skin (100g) and 40% in the muscles (96g), with small amounts being detected in the liver, gut and subcutaneous region [47]. In the serum (intravascular), an average albumin concentration of 45.1–49.9±2.6mg/ml has been reported [46], which approximates to 118g for a typical 70kg bodyweight [44].

Over the last 60 years information concerning the structure of human serum albumin (HSA) has continually been updated and refined. In 1956 Tanford and Buzzell [45] and Loeb and Scheraga [48] described the hydrated protein as a compact spheroid particle, whereas 12 years later Squire et al. [49] reported a cigar-shaped model of 140Å×40Å. This was the accepted textbook model until 1990, when Carter and He presented the first high-resolution crystallographic data for HSA [50]. Using this method at a resolution of 4Å they found a three-dimensional heart-shaped structure for HSA in a crystallized format, which was confirmed 10 years later for bovine serum albumin (BSA) in a hydrated state [51] (Fig. 1).

The shape and physicochemical properties of albumin from human and bovine serum are very similar (Table 1). The secondary structure of albumin consists of three very similar domains (I, II, III) arranged in nine loops with 17 disulfide bridges to stabilize the native form. Each domain has two subdomains (A and B), with subdomain A being composed of six α-helix chains and subdomain B of four α-helix chains. The helices range in size from 5 to 31 amino acids in length [44], [52], [53]. Due to the similarity of HSA and BSA, and the relative availability and lower cost of BSA, many in vitro studies have used BSA as a surrogate for HSA [54], [55], [56].

Table 1. Comparison in structure between HSA and BSA [44]
Molecular weight (Da)Isoionic pointNumber of fatty acids
Human (HSA)66,4385.16585
Bovine (BSA)66,4115.15583

Back to Article Outline

1. Albumin in the preocular tear film 

Far more than 100 different proteins have been identified in the human tear film [40], [57]. Specific tear proteins such as lysozyme, lactoferrin and lipocalin are synthesized by the lacrimal gland; however albumin is a serum protein and becomes mixed with the tear film by leakage from the conjunctival capillaries. The concentration of HSA in the tear film has been investigated by a number of researchers, using a variety of different analytical techniques. In 1993, Bright and Tighe reviewed nine tear film studies and found a vast range of published concentrations, between 0.0103mg/ml and 390mg/ml [58].

Tears may be collected using “stimulated methods”, such as those involving an “eye-flushing” technique or by stimulating a “sneeze”, as compared with an “unstimulated method”, where tears are collected via a capillary tube which does not touch the ocular surface [59], [60], [61], [62]. Generally, higher HSA concentrations are found during sleep [37], [38], [41], in unstimulated tears [37], [59], [61] and in patients with symptoms of dry eye [63], [66], [67] or when wearing contact lenses [38], [64]. Table 2 summarizes typical reported albumin levels in the preocular tear film under various conditions.

Table 2.
Albumin concentration in the tear film (mg/ml)
Nonstimulated tears0.042±0.012 [59]0.023±0.015 [61]0.06±0.02 [37]
Stimulated tears0.012±0.004 [59]0.008±0.001 [65]0.02±0.01 [37]
During sleep0.20 (0.15–0.58) [38]1.1±0.76 [37]1.0±0.5 [41]
Dry eyesIncrease 17% [66]3.7 (0.2–22.6) [63]4.74±0.72 [67]
Wearing contact lenses0.059±0.054 [64] (healthy eye)0.079±0.060 [64] (presence of bacteria on CL)0.54 (0.33–1.24) [38] (wearing Ortho-K CL overnight)

Lundh and coworkers fitted 50 eyes with contact lenses and investigated IgG and HSA concentrations in the tear film. The concentration of both serum proteins increased in 20 eyes, indicating a higher permeability of the blood–tear barrier [68]. The impact of etafilcon A lenses worn on an extended wear schedule on protein levels in the tear film was investigated by Carny et al. [69]. Lactoferrin, lysozyme and HSA levels in collected tears were measured on 10 neophytes before lens wearing and after a period of 6 months. There was a trend for increasing HSA concentration in the tear film over the 6 months of extended wear, but this increase was not statistically significant. In an orthokeratology study, Choy et al. [38] found increasing amounts of HSA, while other tear film proteins (lysozyme, lactoferrin and lipocalin) remained in an unchanged concentration. The ratio between HSA and lactoferrin has also been reported as an indicator for diagnosing primary Sjogren's Syndrome (SS) [70]. Bjerrum measured the protein concentration in patients with connective tissue diseases, SS and controls and concluded that an albumin:lactoferrin ratio above 2:1 is commonly found in patients diagnosed with SS. These findings are of potential significance, since higher protein concentrations in the tear film also appear to lead to increased deposition levels on contact lenses [15], [71], [72], [73].

Back to Article Outline

2. Albumin adhesion to various substrates 

The process of protein adsorption from an aqueous solution onto a solid surface is typically described in three steps. Firstly, transportation of the protein from the solution towards the solid surface occurs. This is followed by attachment of the protein to the surface, and finally the protein structure undergoes a conformational change after adsorption [74]. Carter and Ho investigated the physicochemical properties of HSA and described it as a flexible protein that easily changes its molecular structure [75]. Fluorescent X-ray techniques revealed that the BSA molecules flattened when bound on a gold substrate and the heart-shaped protein, with an initial side length of 3×80Å, increased to a side length of 127Å, with a simultaneous reduction in depth from 30Å to 11.6Å, with this short axis being perpendicular to the solid surface [44], [76]. The amount of HSA that forms a monomolecular layer on most surfaces is approximately 0.15μg/cm2 [77].

Ishiguro and colleagues investigated how lysozyme and BSA deposited and underwent conformational changes on poly tris(trimethylsiloxy)silylstyrene (pTTS), a highly hydrophobic polymer [78]. They reported very different adsorption behavior for the two proteins. Conformational changes of BSA derived strongly from the amount adsorbed to the surface, regardless of soaking time or BSA concentration in the aqueous solution. This was different to lysozyme, where the adsorption time was the leading factor that influenced changes in lysozyme conformation, regardless of the concentration in the solution or the adsorption amount. During the first 15min, BSA adsorption was nearly complete, with only a minor increase occurring over the following 10h, while lysozyme build-up rose significantly over the 10h time period. After adsorption on pTTS, both BSA and lysozyme exhibited smaller α-helix contents and larger contents of β-structure, turn and random coil [78]. Similar findings of conformational changes occurring after short periods of time have been noted for contact lens materials. Garret et al. [79] looked at a variety of contact lens materials and reported changes in the HSA structure when adsorbed to vifilcon A, after as little as 1h of exposure.

Back to Article Outline

3. Albumin adsorption at biomaterial interfaces 

It is clear that albumin is found extensively throughout the body and in the tear film. An understanding of the interaction of this protein with biomaterials is of great importance to understand biocompatibility. Implanted biomaterials are expected to perform a specific task, without being affected by the biological host and without causing side effects such as toxic, carcinogenic, immunogenic or inflammatory responses. Biomaterials are used for contact lenses and a variety of medical applications, including artificial blood vessels, catheters or drug delivery devices [80], [81], [82].

Albumin adsorption is the initial event that occurs after the implant comes into contact with blood serum. The protein is then replaced by immunoglobulin-G, which in turn is replaced by fibrinogen and high molecular weight kininogen. This adsorption and desorption process of blood plasma proteins on artificial surfaces is known as the Vroman effect [83]. It has been shown that platelets can adhere to fibrinogen, which significantly increases the risk of thrombogenesis [84], [85], [86]. It is desirable to have a minimum amount of adsorbed protein onto the biomaterial and, ideally, this uptake should be reversible, with minimal conformational change occurring to the irreversibly adsorbed protein [87], [88], [89]. To improve biocompatibility and minimize the adsorption of fibrinogen and platelets some artificial organs undergo HSA treatment prior to surgery [90].

Within the eye, the aqueous humor of the interior eye has no cellular components and therefore the response to intraocular lenses (IOL) after cataract surgery is mainly affected by the adsorption of various proteins, such as HSA and various globulins [91].

On the ocular surface, deposition of albumin may play a significant role in healthy contact lens wear. Taylor and coworkers demonstrated that increased HSA deposition on etafilcon A lenses resulted in increased adherence of bacteria such as Pseudomonas aeruginosa and Staphylococcus epidermidis [71]. However, the opposite was true for polymacon lenses, with higher HSA deposition being associated with lower bacterial adherence. Other studies have confirmed that some tear-coated contact lens materials enhance adhesion of P. aeruginosa, but high individual variation is always reported [26], [92].

Back to Article Outline

4. Albumin adsorption on contact lens materials 

Contact lenses represent a very specific type of biomaterial interface, in which the material is exposed to both the tear film and various environmental factors. While the level of protein deposition on contact lenses is strongly influenced by the tear composition, it is also modified by the chemical characteristics of the lens material [3], [79], [93], [94]. It has been shown that material composition [17] and properties like water content [1] and pore size [13], [95] roughness of the surface [7], hydrophobicity [3], [17] and charge [25], [73], [94], all play a role, in addition to tear film pH and ionic strength [15], [72]. Finally, protein characteristics such as size, [13] charge [15] and time of material exposure to the protein [1], [2], [3], [4], [5], [8], [15], [16], [20], [22], [78], [79], [93], [96] are all important factors to consider. When patients present with extensively deposited lenses, this deposition will frequently include albumin as a component [1], [12], [22], [24], [27], [42], [43]. However, visual inspection by the clinician will be unable to determine the exact composition of the deposition seen (Fig. 2), with various laboratory-based assays being required to identify individual components.

In vitro, in vivo and ex vivo studies have all been extensively used to describe protein deposition on contact lens materials. During these studies a number of key variables relating to the material under consideration have all proven to be influential in determining the degree to which albumin deposition occurs.

Back to Article Outline

5. Water content 

Soft contact lenses based on polyHEMA are often combined with other monomers and polymers to enhance surface wettability, strength, flexibility and oxygen permeability [97]. In polyHEMA-based hydrogels, increasing water content results in increased oxygen permeability [97], and it has been shown previously that water content can influence the level of protein deposition.

Garrett et al. [13] synthesized a variety of carboxymethylated polyHEMA hydrogels with varying degrees of carboxymethylation, with higher levels of carboxymethylation resulting in lenses with a higher ionic charge and water content. Using a radiolabel-tracer technique they found a clear trend, with increasing water content resulting in decreased amounts of albumin deposition [13]. This is in agreement with the results from Keith et al. [1] who found significant differences in albumin deposition between commercially available contact lenses with low and high water content. All lenses were soaked in an artificial tear solution and two low water content soft lens materials (polyHEMA at 38% water content) exhibited albumin deposition, while no detectable levels of albumin were found on four materials with water contents >55% [1].

Bohnert et al. [3] investigated a variety of commercially available lens materials, in conjunction with a number of polyHEMA materials synthesized with N-vinyl pyrrolidone (NVP), acrylamide (AAM) and methacrylic acid (MAA). They found that the deposition of radiolabeled albumin was similar in materials of varying water content, suggesting that water content alone is not the driving force for albumin deposition [3]. This issue of protein deposition and water content is somewhat complicated, as the deposition is driven by both the charge and water content of the material under consideration, in addition to the size and charge of the depositing protein. In general, lower water content materials tend to deposit proteins such as albumin, in comparison with higher water content materials, which tend to deposit proteins such as lysozyme. This trend is exemplified in the study of Bohnert et al. [3], where lysozyme deposition was greatest on an ionic composition of HEMA–MAA with water contents of 35% and 42%, followed by high water content hydrogels, suggesting that both charge and water content are important. Subbaraman et al. [33] incubated five commercially available polyHEMA-based hydrogel materials over 28 days in lysozyme. He found increasing lysozyme uptake with increasing water content, with the exception of etafilcon A (58% water), which adsorbed multiple times more lysozyme than all other materials. He also reported on five silicone hydrogel (SH) lenses. These materials all deposited significantly less lysozyme than the polyHEMA-based conventional hydrogels and a trend for lower water content SH materials to deposit less lysozyme was also apparent [33].

While some studies indicate that albumin deposition is inversely proportional to water content, others suggest that this is not the case, indicating that water content alone is not the sole driving force for albumin deposition [1], [3], [16], [17], [73], [79].

Back to Article Outline

6. Hydrophobicity 

Hydrogel materials have both hydrophilic and hydrophobic domains, which are influenced by the various monomers used to produce the contact lens material. Factors such as surface wettability and tear film deposition are both markedly affected by the hydrophilicity and hydrophobicity of the lens material. When the surface is covered in a fluid then the surface is orientated such that more hydrophilic components are present at the material interface. In situations where the surface becomes dehydrated (such as that which occurs when the tear film breaks), then chain rotation forces come into play, whereby the hydrophobic polymeric components become reorientated such that they are preferentially expressed on the biomaterial surface. This results in the surface becoming less wettable.

The relatively hydrophobic cross-linking agent ethylene glycol dimethacrylate (EGDMA) is frequently used in the polymerization of polyHEMA. Bajpai and Mishra [73] used a spectrophotometric procedure and reported that increasing concentrations of EGDMA increased albumin deposition. Bohnert et al. [3] synthesized lens materials with various concentrations of relatively hydrophobic MMA and hydrophilic HEMA components and reported that increasing levels of HEMA decreased albumin deposition. In contrast, a study from Pokidysheva et al. [91] investigated four intraocular lenses and they found no significant correlation between hydrophobicity of the material and the level of albumin deposition. However, their results clearly show that hydrophobic PMMA adsorbed the highest level of albumin, and significantly more than polyHEMA, which is in agreement with the other studies described above [98]. However, Barbucci and coworkers synthesized hydrogels with different cross-linking agents to increase the hydrophobic component of the material, and investigated adsorption kinetics and potential denaturing of HSA and fibrinogen using infrared spectroscopy coupled with the attenuated total reflection technique (ATR–FTIR) [98]. They reported a decreasing HSA uptake with increasing hydrophobicity of the material, but the opposite trend was found for fibrinogen with increasing adsorption at increasing hydrophobicity. Furthermore, the hydrophobic character of the material resulted in significantly stronger conformational changes for HSA compared to fibrinogen. It is worthwhile pointing out that the use of different types of cross-linkers might also affect other chemical properties such as strength and pore size of the polymer and not just the hydrophobic nature of the material. Studies have shown that with higher concentrations of cross-linking agents the material modulus increases and the pore sizes decrease making it more difficult for larger proteins to penetrate into the matrix. [99], [100].

In conclusion, the majority of studies report that albumin deposits in higher concentrations on hydrophobic surfaces [7], [18], [79], [94], [98], [101], [102], as compared to relatively hydrophilic surfaces.

Back to Article Outline

7. Charge 

Many studies have investigated the pH of the tear film and a range from 5.2 to 8.6 has been reported [103], [104], with a mean pH value of 7.0–7.5. Therefore, albumin with an isoionic point (iop) of 5.16 has a negative charge in the tear film, as compared with lysozyme (with an iop of 11.4) which has a net positive charge. In general, proteins absorb in maximum amounts on solid surfaces if the solution containing the protein has approximately the same isoionic pH as the protein. This is true for albumin interactions with hydrogels, with the highest albumin uptake occurring at a pH around 5.0 [16], [72], [73] or slightly below [17].

In addition to the pH of the tear film and the polarity of the protein, the relative charge of the material substrate is also highly relevant for the level of deposition. Contact lens materials are categorized in one of four FDA groups, with FDA groups III and IV being considered ionic or negatively charged [97]. PolyHEMA is itself non-ionic, but the addition of monomers such as methacrylic acid, which are commonly used to enhance wettability and/or increase the water content, produces a polymer with an overall net negative charge compared with the tear film. Garrett et al. [13] investigated the effect of ionic charge on the uptake of radiolabeled HSA and lysozyme. Their results showed that increasing the negative charge of the material increased the deposition of positively charged lysozyme and reduced the deposition of negatively charged HSA [13]. In a later study [17], Garrett investigated the deposition on materials containing negatively charged MAA and relatively neutral NVP. Once again, increasing MAA resulted in greater deposition of lysozyme and reduced deposition of albumin. Both radiolabeled proteins adsorbed in higher amounts with increasing NVP concentrations; however the amount of lysozyme detected on the lens was always multiple times higher compared to the albumin uptake [17]. This is in agreement with a study from Moradi et al. [15], where they investigated the same proteins and their interactions with polyHEMA and acrylic acid (AA). As before, the negative AA adsorbed less albumin and more lysozyme than the neutral polyHEMA, which showed higher albumin uptake [15]. Contrary to these findings for lysozyme is the study of Lord et al. [94]. They investigated HSA uptake on polyHEMA, polyHEMA–MAA, polyHEMA–MAA–NVP and PMMA materials using the quartz crystal microbalance with dissipation (QCM-D) technique. They did not find increased lysozyme uptake on the negatively charged polyHEMA–MAA; however, they found the same adsorption pattern for HSA as described in other studies, confirming that HSA adsorbed in highest concentrations to PMMA, followed by polyHEMA–MAA–NVP and polyHEMA, with the lowest albumin uptake reported for the most negatively charged substrate (polyHEMA–MAA) [15]. A further study comparing non-ionic to anionic (negatively charged) and cationic (positively charged) materials was conducted by Soltys-Robitaille et al. [25]. They used matrix assisted laser desorption ionization mass spectrometry (MALDI-ToF MS) and detected albumin on the cationic lens material but not on the pure polyHEMA material. Likewise, lysozyme was detected on the anionic material only [25].

In conclusion, these studies all reveal that electrostatic attraction has a strong impact on albumin deposition. The negatively charged albumin is more likely to deposit on neutral or positively charged substrates than on materials with a net negative charge.

Back to Article Outline

8. Pore size and surface roughness 

Protein penetration into hydrogel materials depends on the pore size and the density of the polymer chains in the material, as well as the structure and size of the protein under consideration. Albumin is known to be a flexible protein which can easily change its original heart-shaped structure (diameter of approximately 55Å) when binding to other molecules such as fatty acids or depositing onto a solid surface [75], [105], [106]. Wood et al. [107] determined the pore size of HEMA with different concentrations of the cross-linker EDGMA. They reported pore diameters of 11.82Å for pure polyHEMA, and even at a maximum concentration of EDGMA of 1.59/104molcm−3 the average pore size only decreased minimally to 11.02Å. Significantly larger pore dimensions were found by Gatin et al. [108]. They used different experimental and simulation techniques to determine the pore size of a polyHEMA-based contact lens and reported an average pore diameter of 428Å. However, most researchers have reported pore sizes <100Å for the surface of various contact lens materials. Gachon et al. [95] reported pore diameters between 56Å and 70.6Å for poly(MMA-VP) lenses, by measuring with a two-dimensional electrophoretic system which proteins can penetrate into hydrogels and which ones are blocked due to the proteins being too large. The two hydrogels examined had identical water contents (70%) and monomer composition, but were sourced from different companies. Albumin was detected in both hydrogels, but the larger protein ceruloplasmin (diameter of 66.2Å) was only found in one of them, indicating the impact of manufacturing on average pore diameter and surface structure. Garrett et al. [13] created two different models to calculate the actual average pore size, based on the water content of the hydrogel material. They added different concentrations of MAA to polyHEMA to increase the water content in the material and calculated the changing pore sizes. For a maximum concentration of 5% MAA they calculated an average pore diameter of 34.7Å and 29.3Å for their two models, and therefore predicted that HSA should not penetrate into their material, which they confirmed experimentally [13]. However, a recent study conducted by Luensmann et al. [109] investigated BSA penetration into a conventional polyHEMA–MAA and a plasma-treated SH contact lens using confocal laser scanning microscopy. They labeled BSA with a fluorescent dye and found increasing BSA uptake into the lens matrix for the polyHEMA material over time, with the SH lens only detecting the fluorescent signal from the labeled protein on the lens surface. This might suggest that the polymer chains were more dense for the SH lens and the pore size on the surface was <55Å, while the surface structure of the polyHEMA lens was looser and/or the average pore size was >55Å. The impact of different techniques for manufacturing polyHEMA contact lenses and albumin adsorption was investigated by Castillo et al. [7]. After an incubation period of 72h they reported a 1.5 times higher HSA uptake on lathe-cut lenses, which provide a rougher surface compared to the spin cast lenses with a smoother surface.

In summary, pore sizes for contact lens materials vary significantly between the polymer composition, manufacturing procedure and the applied measurement technique. It would appear that the average pore size of polyHEMA-based contact lenses is between 20Å and 70Å and that albumin uptake can be mediated by this factor, with larger pore sizes exhibiting greater- and faster-penetration.

Back to Article Outline

9. Temperature and ionic strength 

Albumin deposition decreases with increasing temperature of the solution. Demirel et al. [72] measured the albumin uptake onto hydrogels between 5°C and 40°C and found more than double the amount of albumin deposited at 5°C, as compared to 40°C. They suggested that interactions between the hydrogel and the protein were based on hydrogen bonds, which are weakened with increasing temperature.

Ionic strength of the surrounding media also has an impact on the amount of albumin depositing on the biomaterial. Bajpai and Mishra [73] found decreasing BSA adsorption on polyHEMA with increasing ionic strength of the solution, measured at pH 7.4. However, no such strong tendency was observed by Moradi et al. [15], who investigated the uptake of lysozyme and chicken egg albumin onto polyHEMA and acrylic acid materials by measuring the UV absorbance of the proteins.

Back to Article Outline

10. Conclusion 

Within seconds of insertion, contact lenses are coated with tears, which form a biofilm over the lens surface. This coating, which contains all the components of the tear film, starts to adhere to the lens and progressively increases over time. Increasing levels of HSA in the tear film are found during contact lens wear, especially during overnight wear, and the deposition of HSA is driven by many factors, including the concentration in the tears and the underlying chemical composition of the material being worn. Thus far, most published data have focused on the amount of deposited HSA, and only little is known about its activity and degree of denaturation [78], [79]. Future work should examine the potential impact of denaturation of HSA on immunological responses and clinical consequence of HSA accumulation on contact lenses, as the latest generation of silicone hydrogel materials appears to be deposit only small amounts of protein, but this protein is often denatured [33], [110].

From this review, it can be concluded that many factors impact the adsorption of albumin onto hydrogel and PMMA lens materials. The higher the concentration of albumin in the tear film the greater the degree of deposition that can be expected on the lens material, particularly if the lens is worn overnight, or the patient exhibits dry eye or ocular surface disease. In addition, a larger pore size of the lens polymer will also increase albumin absorption. However, albumin deposition can be minimized if the material exhibits a net negative charge, is relatively hydrophilic and exhibits a high water content. Given these characteristics, deposition on silicone hydrogels, which now comprise a significant proportion of the lens materials fitted worldwide [111], [112], is to be expected and the deposition of albumin and its activity on silicone hydrogels should be a focus of future work.

Back to Article Outline

References 

  1. Keith D, Hong B, Christensen M. A novel procedure for the extraction of protein deposits from soft hydrophilic contact lenses for analysis. Curr Eye Res. 1997;16(5):503–510
  2. Brennan NA, Coles ML, Comstock TL, Levy B. A 1-year prospective clinical trial of balafilcon a (PureVision) silicone-hydrogel contact lenses used on a 30-day continuous wear schedule. Ophthalmology. 2002;109(6):1172–1177
  3. Bohnert JL, Horbett TA, Ratner BD, Royce FH. Adsorption of proteins from artificial tear solutions to contact lens materials. Invest Ophthalmol Vis Sci. 1988;29(3):362–373
  4. Baines MG, Cai F, Backman HA. Adsorption and removal of protein bound to hydrogel contact lenses. Optom Vis Sci. 1990;67(11):807–810
  5. Gachon AM, Bilbaut T, Dastugue B. Adsorption of tear proteins on soft contact lenses. Exp Eye Res. 1985;40(1):105–116
  6. Tripathi PC, Tripathi RC. Analysis of glycoprotein deposits on disposable soft contact lenses. Invest Ophthalmol Vis Sci. 1992;33(1):121–125
  7. Castillo EJ, Koenig JL, Anderson JM, Lo J. Characterization of protein adsorption on soft contact lenses. I. Conformational changes of adsorbed human serum albumin. Biomaterials. 1984;5(6):319–325
  8. Castillo EJ, Koenig JL, Anderson JM. Characterization of protein adsorption on soft contact lenses IV. Comparison of in vivo spoilage with the in vitro adsorption of tear proteins. Biomaterials. 1986;7(2):89–96
  9. Michaud L, Giasson C. Comparing the extent of protein build-up on several disposable lenses by two spectrophotometric methods. Cont Lens Anterior Eye. 1998;21(4):104–108
  10. Mannucci LL, Moro F, Cosani A, Palumbo M. Conformational state of lacrimal proteins adsorbed on contact lenses. Curr Eye Res. 1985;4(6):734–736
  11. Keith DJ, Christensen MT, Barry JR, Stein JM. Determination of the lysozyme deposit curve in soft contact lenses. Eye Contact Lens. 2003;29(2):79–82
  12. Brennan NA, Coles ML. Deposits and symptomatology with soft contact lens wear. Int Contact Lens Clin. 2000;27:75–100
  13. Garrett Q, Chatelier RC, Griesser HJ, Milthorpe BK. Effect of charged groups on the adsorption and penetration of proteins onto and into carboxymethylated poly(HEMA) hydrogels. Biomaterials. 1998;19(23):2175–2186
  14. Richard NR, Anderson JA, Tasevska ZG, Binder PS. Evaluation of tear protein deposits on contact lenses from patients with and without giant papillary conjunctivitis. Clao J. 1992;18(3):143–147
  15. Moradi O, Modarress H, Noroozi M. Experimental study of albumin and lysozyme adsorption onto acrylic acid, (AA) and 2-hydroxyethyl methacrylate (HEMA) surfaces. J Colloid Interface Sci. 2004;271(1):16–19
  16. Garrett Q, Milthorpe BK. Human serum albumin adsorption on hydrogel contact lenses in vitro. Invest Ophthalmol Vis Sci. 1996;37(13):2594–2602
  17. Garrett Q, Laycock B, Garrett RW. Hydrogel lens monomer constituents modulate protein sorption. Invest Ophthalmol Vis Sci. 2000;41(7):1687–1695
  18. Park JH, Bae YH. Hydrogels based on poly, (ethylene oxide) and poly, (tetramethylene oxide) or poly, (dimethyl siloxane): synthesis, characterization, in vitro protein adsorption and platelet adhesion. Biomaterials. 2002;23(8):1797–1808
  19. Zhang S, Borazjani RN, Salamone JC, Ahearn DG, Crow SA, Pierce GE. In vitro deposition of lysozyme on etafilcon A and balafilcon A hydrogel contact lenses: effects on adhesion and survival of Pseudomonas aeruginosa and Staphylococcus aureus. Cont Lens Anterior Eye. 2005;28(3):113–119
  20. Jones L, Senchyna M, Glasier MA, Schickler J, Forbes I, Louie D, et al. Lysozyme and lipid deposition on silicone hydrogel contact lens materials. Eye Contact Lens. 2003;29(1 Suppl):S75–S79discussion S83–4, S192–4
  21. Kingshott P, St John HA, Chatelier RC, Griesser HJ. Matrix-assisted laser desorption ionization mass spectrometry detection of proteins adsorbed in vivo onto contact lenses. J Biomed Mater Res. 2000;49(1):36–42
  22. Lin ST, Mandell RB, Leahy CD, Newell JO. Protein accumulation on disposable extended wear lenses. Clao J. 1991;17(1):44–50
  23. Minno GE, Eckel L, Groemminger S, Minno B, Wrzosek T. Quantitative analysis of protein deposits on hydrophilic soft contact lenses: I. Comparison to visual methods of analysis. II. Deposit variation among FDA lens material groups. Optom Vis Sci. 1991;68(11):865–872
  24. Pearce D, Tan ME, Demirci G, Willcox MD. Surface protein profile of extended-wear silicon hydrogel lenses. Adv Exp Med Biol. 2002;506(Pt B):957–960
  25. Soltys-Robitaille CE, Ammon DM, Valint PL, Grobe GL. The relationship between contact lens surface charge and in-vitro protein deposition levels. Biomaterials. 2001;22(24):3257–3260
  26. Bruinsma GM, Rustema-Abbing M, de Vries J, Stegenga B, van der Mei HC, van der Linden ML, et al. Influence of wear and overwear on surface properties of etafilcon A contact lenses and adhesion of Pseudomonas aeruginosa. Invest Ophthalmol Vis Sci. 2002;43(12):3646–3653
  27. Vermeltfoort PB, Rustema-Abbing M, de Vries J, Bruinsma GM, Busscher HJ, van der Linden ML, et al. Influence of day and night wear on surface properties of silicone hydrogel contact lenses and bacterial adhesion. Cornea. 2006;25(5):516–523
  28. Lorentz H, Jones L. Lipid deposition on hydrogel contact lenses: how history can help us today. Optom Vis Sci. 2007;84(4):286–295
  29. Maziarz EP, Stachowski MJ, Liu XM, Mosack L, Davis A, Musante C, et al. Lipid deposition on silicone hydrogel lenses, part I: quantification of oleic acid, oleic acid methyl ester, and cholesterol. Eye Contact Lens. 2006;32(6):300–307
  30. Spurr-Michaud S, Argueso P, Gipson I. Assay of mucins in human tear fluid. Exp Eye Res. 2007;84(5):939–950
  31. Yan G, Nyquist G, Caldwell KD, Payor R, McCraw EC. Quantitation of total protein deposits on contact lenses by means of amino acid analysis. Invest Ophthalmol Vis Sci. 1993;34(5):1804–1813
  32. Santos L, Rodrigues D, Lira M, Oliveira ME, Oliveira R, Vilar EY, et al. The influence of surface treatment on hydrophobicity, protein adsorption and microbial colonisation of silicone hydrogel contact lenses. Cont Lens Anterior Eye. 2007;
  33. Subbaraman LN, Glasier MA, Senchyna M, Sheardown H, Jones L. Kinetics of in vitro lysozyme deposition on silicone hydrogel, PMMA, and FDA groups I, II, and IV contact lens materials. Curr Eye Res. 2006;31(10):787–796
  34. Senchyna M, Jones L, Louie D, May C, Forbes I, Glasier MA. Quantitative and conformational characterization of lysozyme deposited on balafilcon and etafilcon contact lens materials. Curr Eye Res. 2004;28(1):25–36
  35. Temel A, Kazokoglu H, Taga Y. Tear lysozyme levels in contact lens wearers. Ann Ophthalmol. 1991;23(5):191–194
  36. Zhou L, Beuerman RW, Foo Y, Liu S, Ang LP, Tan DT. Characterisation of human tear proteins using high-resolution mass spectrometry. Ann Acad Med Singapore. 2006;35(6):400–407
  37. Sack RA, Tan KO, Tan A. Diurnal tear cycle: evidence for a nocturnal inflammatory constitutive tear fluid. Invest Ophthalmol Vis Sci. 1992;33(3):626–640
  38. Choy CK, Cho P, Benzie IF, Ng V. Effect of one overnight wear of orthokeratology lenses on tear composition. Optom Vis Sci. 2004;81(6):414–420
  39. Sitaramamma T, Shivaji S, Rao GN. HPLC analysis of closed, open, and reflex eye tear proteins. Indian J Ophthalmol. 1998;46(4):239–245
  40. de Souza GA, Godoy LM, Mann M. Identification of 491 proteins in the tear fluid proteome reveals a large number of proteases and protease inhibitors. Genome Biol. 2006;7(8):R72
  41. Tan KO, Sack RA, Holden BA, Swarbrick HA. Temporal sequence of changes in tear film composition during sleep. Curr Eye Res. 1993;12(11):1001–1007
  42. Bilbaut T, Gachon AM, Dastugue B. Deposits on soft contact lenses electrophoresis and scanning electron microscopic examinations. Exp Eye Res. 1986;43(2):153–165
  43. Scott G, Mowrey-McKee M. Dimerization of tear lysozyme on hydrophilic contact lens polymers. Curr Eye Res. 1996;15(5):461–466
  44. Peters T. All about albumin: biochemistry, genetics, and medical applications. San Diego, Calif: Academic Press; 1996;xx, 432 [2] of plates
  45. Tanford C, Buzzell JG. The viscosity of aqueous solutions of bovine serum albumin between pH 4.3 and 10.5. J Phys Chem. 1956;60:225–231
  46. Hostmark AT, Tomten SE, Berg JE. Serum albumin and blood pressure: a population-based, cross-sectional study. J Hypertens. 2005;23(4):725–730
  47. Doweiko JP, Nompleggi DJ. Role of albumin in human physiology and pathophysiology. JPEN J Parenter Enteral Nutr. 1991;15(2):207–211
  48. Loeb GI, Scheraga HA. Hydrodynamic and thermodynamic properties of bovine serum albumin at low pH. J Phys Chem. 1956;60:1633–1644
  49. Squire PG, Moser P, O’Konski CT. The hydrodynamic properties of bovine serum albumin monomer and dimer. Biochemistry. 1968;7(12):4261–4272
  50. Carter DC, He XM. Structure of human serum albumin. Science. 1990;249(4966):302–303
  51. Ferrer ML, Duchowicz R, Carrasco B, de la Torre JG, Acuna AU. The conformation of serum albumin in solution: a combined phosphorescence depolarization-hydrodynamic modeling study. Biophys J. 2001;80(5):2422–2430
  52. Sugio S, Kashima A, Mochizuki S, Noda M, Kobayashi K. Crystal structure of human serum albumin at 2, 5 A resolution. Protein Eng. 1999;12(6):439–446
  53. He XM, Carter DC. Atomic structure and chemistry of human serum albumin. Nature. 1992;358(6383):209–215
  54. Michnik A, Michalik K, Drzazga Z, Kluczewska A. Comparative DSC Study of human and bovine serum albumin. J Therm Anal Cal. 2007;84(1):113–117
  55. Kurrat R, Prenosil JE, Ramsden JJ. Kinetics of human and bovine serum albumin adsorption at silica-titania surfaces. J Colloid Interface Sci. 1997;185(1):1–8
  56. Miller I, Gemeiner M. Peculiarities in electrophoretic behavior of different serum albumins. Electrophoresis. 1993;14(12):1312–1317
  57. Fung K, Morris C, Duncan M. Mass spectrometric techniques applied to the analysis of human tears: a focus on the peptide and protein constituents. Adv Exp Med Biol. 2002;506(Pt A):601–605
  58. Bright AM, Tighe BJ. The composition and interfacial properties of tears, tear substitutes and tear models. J Br Contact Lens Assoc. 1993;16(2):57–66
  59. Fullard RJ, Snyder C. Protein levels in nonstimulated and stimulated tears of normal human subjects. Invest Ophthalmol Vis Sci. 1990;31(6):1119–1126
  60. Ng V, Cho P. The relationship between total tear protein concentrations determined by different methods and standards. Graefes Arch Clin Exp Ophthalmol. 2000;238(7):571–576
  61. Ng V, Cho P, Mak S, Lee A. Variability of tear protein levels in normal young adults: between-day variation. Graefes Arch Clin Exp Ophthalmol. 2000;238(11):892–899
  62. Bjerrum KB, Prause JU. Collection and concentration of tear proteins studied by SDS gel electrophoresis presentation of a new method with special reference to dry eye patients. Graefes Arch Clin Exp Ophthalmol. 1994;232(7):402–405
  63. Van Bijsterveld OP, Janssen PT. Local antibacterial defense in the sicca syndrome. In:  Holly FJ,  Lamberts DW,  MacKeen DL editor. The preocular tear film in health, disease and contact lens wear. Lubbock, Texas: Dry Eye Institute, Inc.; 1986;p. 857–864
  64. Baleriola-Lucas C, Fukuda M, Willcox MD, Sweeney DF, Holden BA. Fibronectin concentration in tears of contact lens wearers. Exp Eye Res. 1997;64(1):37–43
  65. Fullard RJ, Tucker DL. Changes in human tear protein levels with progressively increasing stimulus. Invest Ophthalmol Vis Sci. 1991;32(8):2290–2301
  66. Mandel ID, Stuchell RN. The lacriamal-salivary axis in health and disease. In:  Holly FJ,  Lamberts DW,  MacKeen DL editor. The preocular tear film in health, disease and contact lens wear. Dry Eye Institute, Inc.: Lubbock, Texas; 1986;p. 852–856
  67. van Bijsterveld OP, Janssen PT. The effect of calcium dobesilate on albumin leakage of the conjunctival vessels. Curr Eye Res. 1981;1(7):425–430
  68. Lundh RL, Liotet S, Pouliquen Y. Study of the human blood-tear barrier and the biochemical changes in the tears of 30 contact lens wearers (50 eyes). Ophthalmologica. 1984;188(2):100–105
  69. Carney FP, Morris CA, Willcox MD. Effect of hydrogel lens wear on the major tear proteins during extended wear. Aust N Z J Ophthalmol. 1997;25(Suppl. 1):S36–S38
  70. Bjerrum KB. The ratio of albumin to lactoferrin in tear fluid as a diagnostic tool in primary Sjogren's syndrome. Acta Ophthalmol Scand. 1997;75(5):507–511
  71. Taylor RL, Willcox MD, Williams TJ, Verran J. Modulation of bacterial adhesion to hydrogel contact lenses by albumin. Optom Vis Sci. 1998;75(1):23–29
  72. Demirel G, Ozcetin G, Turan E, Caykara T. pH/temperature - sensitive imprinted ionic poly, (N-tert-butylacrylamide-co-acrylamide/maleic acid) hydrogels for bovine serum albumin. Macromol Biosci. 2005;5(10):1032–1037
  73. Bajpai AK, Mishra DD. Adsorption of a blood protein on to hydrophilic sponges based on poly (2-hydroxyethyl methacrylate). J Mater Sci Mater Med. 2004;15(5):583–592
  74. Dijt JC, Cohen-Stuart MA, Hofman JE, Fleer GJ. Kinetics of polymer adsorption in stagnation point flow. Colloids Surfaces. 1990;51:141–158
  75. Carter DC, Ho JX. Structure of serum albumin. Adv Protein Chem. 1994;45:153–203
  76. Sasaki Y, Suzuki Y, Ishibashi T. Fluorescent X-ray interference from a protein monolayer. Science. 1994;263(5143):62–64
  77. Mura-Galelli MJ, Voegel JC, Behr S, Bres EF, Schaaf P. Adsorption/desorption of human serum albumin on hydroxyapatite: a critical analysis of the Langmuir model. Proc Natl Acad Sci U S A. 1991;88(13):5557–5561
  78. Ishiguro R, Yokoyama Y, Maeda H, Shimamura A, Kameyama K, Hiramatsu K. Modes of conformational changes of proteins adsorbed on a planar hydrophobic polymer surface reflecting their adsorption behaviors. J Colloid Interface Sci. 2005;290(1):91–101
  79. Garrett Q, Griesser HJ, Milthorpe BK, Garrett RW. Irreversible adsorption of human serum albumin to hydrogel contact lenses: a study using electron spin resonance spectroscopy. Biomaterials. 1999;20(14):1345–1356
  80. Peppas NA. Hydrogels in medicine and pharmacy.. Boca Raton, Fla: CRC Press; 1986;
  81. Peppas NA, Huang Y, Torres-Lugo M, Ward JH, Zhang J. Physicochemical foundations and structural design of hydrogels in medicine and biology. Annu Rev Biomed Eng. 2000;2:9–29
  82. Hoffman AS. Hydrogels for biomedical applications. Adv Drug Deliv Rev. 2002;54(1):3–12
  83. Vroman L, Adams AL, Fischer GC, Munoz PC. Interaction of high molecular weight kininogen, factor XII, and fibrinogen in plasma at interfaces. Blood. 1980;55(1):156–159
  84. Mandrusov E, Yang JD, Pfeiffer N, Vroman L, Puszkin P, Leonard EF. Kinetics of protein deposition and replacement from a shear flow. AIChE J. 1998;44(2):233–244
  85. Morrissey BW. The adsorption and conformation of plasma proteins: a physical approach. Annals of the New York Academy of Sciences. 1977;283(1):50–64
  86. Missirlis YF, Lemm W. Modern aspects of protein adsorption on biomaterials. vol. x. Dordrecht: Kluwer Academic Publishers; 1991;p. 262
  87. Park H, Park K. Biocompatibility issues of implantable drug delivery systems. Pharm Res. 1996;13(12):1770–1776
  88. Ratner BD. Biomaterials science: an introduction to materials in medicine Blood coagulation and blood-materials interactions. San Diego; London: Academic Press; 1996;pp. 193–199
  89. Pitt WG, Park K, Cooper SL. Sequential protein adsorption and thrombus deposition on polymeric biomaterials. J Colloid Interface Sci. 1986;111(2):343–362
  90. Brynda E, Houska M, Jirouskova M, Dyr JE. Albumin and heparin multilayer coatings for blood-contacting medical devices. J Biomed Mater Res. 2000;51(2):249–257
  91. Pokidysheva EN, Maklakova IA, Belomestnaya ZM, Perova NV, Bagrov SN, Sevastianov VI. Comparative analysis of human serum albumin adsorption and complement activation for intraocular lenses. Artif Organs. 2001;25(6):453–458
  92. Miller MJ, Wilson LA, Ahearn DG. Effects of protein, mucin, and human tears on adherence of Pseudomonas aeruginosa to hydrophilic contact lenses. J Clin Microbiol. 1988;26(3):513–517
  93. Willcox M, Pearce D, Tan M, Demirci G, Carney F. Contact lenses and tear film interactions. Adv Exp Med Biol. 2002;506(Pt B):879–884
  94. Lord MS, Stenzel MH, Simmons A, Milthorpe BK. The effect of charged groups on protein interactions with poly (HEMA) hydrogels. Biomaterials. 2006;27(4):567–575
  95. Gachon AM, Bilbault T, Dastugue B. Protein migration through hydrogels: a tool for measuring porosity—application to hydrogels used as contact lenses. Anal Biochem. 1986;157(2):249–255
  96. Garrett Q, Garrett RW, Milthorpe BK. Lysozyme sorption in hydrogel contact lenses. Invest Ophthalmol Vis Sci. 1999;40(5):897–903
  97. Tighe B. In:  Phillips F,  Speedwell L editor. Contact lens materials, in contact lenses. Butterworth-Heinemann: Edinburgh; 2006;p. 59–78
  98. Barbucci R, Magnani A, Leone G. The effects of spacer arms in cross-linked hyaluronan hydrogel on Fbg and HSA adsorption and conformation. Polymer. 2002;43(12):3541–3548
  99. Novick SJ, Dordick JS. Investigating the effects of polymer chemistry on activity of biocatalytic plastic materials. Biotechnol Bioeng. 2000;68(6):665–671
  100. Gomez CG, Alvarez Igarzabal CI, Strumia MC. Effect of the crosslinking agent on porous networks formation of hema-based copolymers. Polymer. 2004;45(18):6189–6194
  101. Kita M, Ogura Y, Honda Y, Hyon SH, Cha W, Ikada Y. Evaluation of polyvinyl alcohol hydrogel as a soft contact lens material. Graefes Arch Clin Exp Ophthalmol. 1990;228(6):533–537
  102. Kim J, Somorjai GA. Molecular packing of lysozyme, fibrinogen, and bovine serum albumin on hydrophilic and hydrophobic surfaces studied by infrared-visible sum frequency generation and fluorescence microscopy. J Am Chem Soc. 2003;125(10):3150–3158
  103. Abelson MB, Udell IJ, Weston JH. Normal human tear pH by direct measurement. Arch Ophthalmol. 1981;99(2):301
  104. Yamada M, Mochizuki H, Kawai M, Yoshino M, Mashima Y. Fluorophotometric measurement of pH of human tears in vivo. Curr Eye Res. 1997;16(5):482–486
  105. Curry S, Mandelkow H, Brick P, Franks N. Crystal structure of human serum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites. Nat Struct Biol. 1998;5(9):827–835
  106. Rodbard D, Chrambach A. Estimation of molecular radius, free mobility, and valence using polyacylamide gel electrophoresis. Anal Biochem. 1971;40(1):95–134
  107. Wood JM, Attwood D, Collett JH. Characterization of poly, (2-hydroxyethyl methacrylate) gels. Marcel Dekkr, Inc.; 1983;p. 93–101
  108. Gatin E, Alexandreanu D, Popescu A, Berlic C, Alexandreanu I. Correlations between permeability properties and the pore-size distribution of the porous media “hydron” useful as contact lenses. Phusica Med. 1999;XVI(1):13–19
  109. Luensmann D, Glasier MA, Zhang F, Bantseev V, Simpson T, Jones L. Confocal microscopy and albumin penetration into contact lenses. Optom Vis Sci. 2007;84(9):839–847
  110. Suwala M, Glasier MA, Subbaraman LN, Jones L. Quantity and conformation of lysozyme deposited on conventional and silicone hydrogel contact lens materials using an in vitro model. Eye Contact Lens. 2007;33(3):138–143
  111. Woods CA, Jones DA, Jones LW, Morgan PB. A seven year survey of the contact lens prescribing habits of Canadian optometrists. Optom Vis Sci. 2007;84(6):505–510
  112. Morgan PB, Efron N. A decade of contact lens prescribing trends in the United Kingdom (1996–2005). Cont Lens Anterior Eye. 2006;29(2):59–68

PII: S1367-0484(08)00072-6

doi:10.1016/j.clae.2008.05.004

Contact Lens & Anterior Eye
Volume 31, Issue 4 , Pages 179-187, August 2008

Article Tools

* Image Usage & Resolution