But what in the world is a "Cataract?" Did you know over 50% of Americans over 75 have Cataracts? Lanosterol J. Membr. You are using a browser version with limited support for CSS. The target proteins were three B-crystallins obtained from the Protein Data Bank (PDB): a human wild type dimer 2WJ741, a human wild type B-crystallin 2KLR42, and a R120G mutant, 2Y1Z43. Kador, P. F., Wyman, M. & Oates, P. J. Aldose reductase, ocular diabetic complications and the development of topical Kinostat((R). Therefore, additional in silico studies to gain insight into chaperone binding to lanosterol and 25-hydroxycholesterol at the molecular level were conducted. EMBO J. In vitro organ culture of lenses has become a powerful experimental tool for not only investigating the relationship between lens metabolism and lens clarity, but also for elucidating the mechanism(s) of cataract formation by drugs and biochemical agents47,58. Peter F. Kador. The lanosterol sheets were converted to liposomes by sonication using a micro homogenizer tip (MISONIX Fisher Scientific Sonicator Ultrasonic Processor XL) until the solution appeared homogenous (~5min). After 48hours the culture media for each lens was replaced with fresh TC-199 bicarbonate media containing 15mM of lanosterol liposomes and the lenses were cultured an additional 48hours. Steroids. Cataract, a crystallin aggregation disease, is the leading cause of human blindness worldwide. ISSN 2045-2322 (online). The complex peak showed no significant change in the molar mass (MW) or hydrodynamic radii (Rh) of B-crystallin incubated with 25-hydroxycholesterol. Learn About The Eye-Drop effective in reversing Cataracts Widomska, J., Subczynski, W. K., Mainali, L. & Raguz, M. Cholesterol Bilayer Domains in the Eye Lens Health: A Review. Ophthalmic epidemiol. 3rd Use of dynamic light scattering and Scheimpflug imaging for the early detection of cataracts. 62, 16J27J (1988). Among these are the small heat shock proteins (sHSP) -crystallins with chaperone-like activity that play a central role in maintaining lens transparency by trapping the denaturing or unfolding proteins that are responsible for light scattering in the highly ordered lens fibers14,15,16,17. Philos Trans R Soc Lond B Biol Sci. Proc Natl Acad Sci USA 89, 1044910453 (1992). Biol. Again, adequate binding values for ATP binding to the ATP binding pocket of the wild-type 2WJ7 and 2Y1Z mutant models were obtained; however, oxysterols were not able to bind to the ATP binding pockets of these B-crystallins. Similarly, the open-structure observed in wild type 2WJ7 is disrupted in the ARG120GLY mutation 2Y1Z so that the mutation of ARG120 to GLY makes it impossible to form a stabilizing salt bridge between ARG120 and ASP109. This is not surprising since natural selection has preferred ATP to bind to the ATP binding pocket. Lanomax: An In-Depth Look at Lanosterol Eye Drops - DR Vitamin Solutions APPLICATIONFIRST, SHAKE GENTLY BEFORE EACH APPLICATION. 10; Lanosterol treatment reduced cataract severity and increased transparency in rabbits and dogs. Similarly, clinically administering eye drops containing 5mM lanosterol dissolved in olive oil two times daily for the first week and three times daily for the next seven weeks to a patient with idiopathic unilateral juvenile nuclear cataracts failed to produce any relevant clinical effect in reversing either the cataract or halting the progressive worsening of visual acuity with an increasing of myopic shift31. Google Scholar. Cataracts affect vision and cause images to appear cloudy, fuzzy, or blurry. J Ophthalmol. Further research has confirmed that simple lanosterol solutions alone are ineffective at permeating the lens of the eye and having a dissolving effect on cataract formations. 7, 501515 (2016). Six frozen lenses from 60-year-old donors were each cut into three equal pie shapes with each sample composed of two pie shapes from different lenses. Invest Ophthalmol Vis Sci. This indicates that the methods employed successfully predicted the expected feasible nanomolar range binding of ATP to the ATP binding pocket of these chaperones. BMC Med Genet. 9, 887892 (2009). 506, 868873 (2018). Osmotic stress, not aldose reductase activity, directly induces growth factors and MAPK signaling changes during sugar cataract formation. 156, 5057 (2017). (MER-29). This binding mode has also been found in several ATP-binding proteins, including HSP90 and HSP10445,46. Lanomax is the only eye drop on the planet currently that has a real therapeutic effect on cataracts. If approved for human use, the compound would be available as a non-invasive treatment for individuals with . Environ Toxicol Pharmacol. The mammalian lens contains millions of densely packed fiber cells that are continuously formed throughout life from differentiating lens epithelial cells. 2011;366(1568):12781292. & Donaldson, P. The lens circulation. At the end of the incubation, the tubes were centrifuged at 13,000rpm for 15min at 4C. A clear life is a quality lifeHelp your canine live cataract-free with Plush Paws Advanced Lanosterol Solution + NAC. For the patient with a cataract, the presence of lanosterol in the lacrimal fluid reduced the cadmium and lead dissolution currents by 20% and reduced the cobalt and mercury dissolution currents by 50% (Fig. Shanmugam, P. M. et al. The Chemical Computing Groups Molecular Operating Environment 2016 (MOE) and Schrdinger LLCs program, Maestro 11, were used for this study. Similarly, Shen et al. Mathias, R. T. & Rae, J. L. Transport properties of the lens. Samples incubated only with 10% ethanol served as controls. Article In addition, the Walker-B ATP-binding motifs containing the sequence 82KHFSPEELKVKVLGD96 were used for docking on both wildtypes, 2WJ7 and 2KLR and mutant 2Y1Z to determine whether the oxysterols can also bind to the ATP binding pocket. To address this question, docking studies with ATP, 25-hydroxycholesterol and lanosterol were also conducted using the Glide dock program to the 4-8 groove, which is the ATP interactive binding region, as well as the dimer interface containing the PHE 55 centroid (Table2). Another study showed that a natural steroid known as lanosterol reduces cataract severity in animals. & Augusteyn, R. C. Binding of dexamethasone by alpha-crystallin. Provided by the Springer Nature SharedIt content-sharing initiative. It's similar to looking through a foggy window. For 25-hydroxycholesterol, the predicted Kd values were between 4.4mM and 27.6mM for the 2WJ7 and 2Y1Z model, respectively. 48, 889902 (2004). 43, 955963 (1986). They saw a significant decrease. 408, 118134 (2011). Binding results for lanosterol in the dimer interface were even worse, with Kd values for 2WJ7 and 2KLR of 3.55mM and 73.63mM obtained; Kd values for 2Y1Z could not be determined. 7). However, ATP binding to mutant 2Y1Z appeared to be lower as suggested by the lower docking score (9.82kcal/mol). Here we identify two distinct homozygous LSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts. Article By clicking Accept All Cookies, you agree to the storing of cookies on your device to enhance site navigation, analyze site usage, and assist in our marketing efforts. If material is not included in the articles Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Proctor Lecture. 2). As illustrated in Fig. Glide dock docking scores (Table2) for 2KLR and 2Y1Z models gave ATP binding scores (5.57kcal/mol at the ATP pocket of 2KLR and the interface of 2KLR and 2Y1Z) that were in good agreement with Palmisano et al.79 who determined the binding constant for ATP to the -crystallin to be (Ka=8.1 * 103M1 which corresponds to 5.33kcal/mol when converted to G). Exp Eye Res. 38, 23132321 (1997). Cheng, Q. F., Rao, P. V. & Zigler, J. S. Jr. Effect of perillic acid, a putative isoprenylation inhibitor, on the cultured rat lens. Hong, M. G., Jiang, S. Y. 73, 239245 (2001). 366, 12501264 (2011). D.M.D., P.S. Mar 2006. Qi, L. B. et al. We defined the same binding pocket for the 2KLR wildtype, and PHE 118 was identified as the centroid for the R120G mutant dimer, 2Y1Z. And indeed, after. To confirm this premise, in vitro rat lens studies along with human lens protein solubilization studies were conducted. Pharmacological chaperone for alpha-crystallin partially restores transparency in cataract models. 523, 540541 (2015). 34, 1022 (1993). Locations of the defined ATP pocket and PHE 55 binding regions for docking studies are marked with arrows on the ribbon structures. A later study failed to support the finding that lanosterol improves lens clarity for those with cataracts. To test that, they grew lens cells with crystallin clumps in a Petri dish. A ligand with a Kd above 10M (dock score: worse than 6.8) is normally considered to be low affinity. Preclinical evaluation of lovastatin. 2), the amber appearance of the cortex and surrounding nucleus in the cataractous lenses does not rule out the possibility that the appearance is due only to the presence of liposomes in the extracellular space between the lens fibers. In Makley et al., 100M concentration of drugs were used and at this concentration, 56% recovery vs wild-type in Tm was observed24. Vet Ophthalmol. The Maestro docking studies were conducted using Glide Dock by first defining the binding pocket using the Glide Grid Generation method using centroids identified above for all three proteins, wildtypes 2WJ7 and 2KLR and the R120G mutant 2Y1Z, followed by Glide dock with scoring function of Extra Precision (XP). Once the binding pocket was identified, ligands were docked to the binding site using MOE docking with the Triangle Matcher placement and the flexible Induced Fit method. The appearance of each lens was immediately photo-documented by placing the lens over a light source containing a grid. The docking scores of each protein-ligand docked complex were expressed in kcal/mol, with 9 kcal/mol approximated to an IC50 or Kd in the high nM/low M range. Philos Trans R Soc Lond B Biol Sci. (2) B-crystallin (2.0mg/mL) in PBS. Molecular modeling and docking studies were conducted using MOE dock and Schrdinger Glide dock standard docking methods. Moreau, K. L. & King, J. The combined power of lanosterol and N-acetylcarnosine helps clear cloudiness caused by cataracts and provides antioxidant support ; : As pets age, cataracts are common. While the oxysterol indeed appears to solubilize in the B-crystallin solution, subsequent multi-angle light scattering (MALS) analysis indicates that the 25-hydroxycholesterol becomes trapped within the oligomers of B-crystallin. One of these, known as lanosterol, was shown to reverse cataracts in a June paper in Nature, but because lanosterol has limited solubility the group who published that study had to inject the compound into the eye for it to exert its effects. J Ophthalmol. 3 Altmetric Metrics Abstract Cataract, the leading cause of vision impairment worldwide, arises from abnormal aggregation of crystallin lens proteins. Zigler, J. S. Jr., Gery, I., Kessler, D. & Kinoshita, J. H. Macrophage mediated damage to rat lenses in culture: a possible model for uveitis-associated cataract. Eye Drops for Cataracts Treatment: What You Need to Know 2015;523(7562):607-11. doi:10.1038/nature14650, Shen X, Zhu M, Kang L, et al. ADD TO CART . and A.S.P. Ray, N. J. Biophysical chemistry of the ageing eye lens. The function of alpha-crystallin. They will check your eyes to make sure you aren't developing an infection and make sure your eyes are healing properly. Failure of oxysterols such as lanosterol to restore lens clarity from cataracts. At present, the relationship between the regulation of cholesterol-dependent processes in lens fiber cells and their plasma membranes and cataract formation is not well established and more studies in this area are required. In contrast to ATP, the present MOE and Glide docking scores suggest that lanosterol and 25-hydroxycholesterol binding to -crystallin is unlikely at less than micromolar concentrations. This work was supported by a Purdue Pharma Scholarship and a University of Nebraska Medical Center Graduate Student Fellowship. Tissue homogenates from 72 year old human lenses containing 0.5 or 2.0mg protein in 1.0mL of PBS were incubated with 0.0, 100 and 200M lanosterol or 25-hydroxycholesterol at 37C for 24hours. & Vrensen, G. F. Biological glass: structural determinants of eye lens transparency. Although lens lanosterol levels were never specifically measured after triparanol administration, it can be assumed that downstream inhibition of cholesterol synthesis would similarly increase lanosterol levels in the lens. A Future Alternative to Cataract Surgery? 29, 174179 (2001). 2019;60(9):5691. It has also led to the commercialization of lanosterol eye drops27,28,29. 2016;113(1):5862. Lanosterol Eye Drops for Cataracts | MyVision.org and A.S.P. 58, 367374 (1994). The human lens is composed of crystalline proteins. Metabolism. Sci Rep 9, 8459 (2019). Cite this article. Oxidative stress is among the main mechanisms involved in the development of age-related cataract. Bassnett, S. & Costello, M. J. CAS Output was a London G binding score. However, achieving similar binding results for the oxysterols was more difficult. Felici, A., Mengato, D., Falciani, M. & Bertelli, E. Lanosterol Eye Drops in a Human Juvenile Nuclear Cataract. J Lipid Res. Rao, P. V. et al. These elongated fiber cells become completely internalized with their ends joined by collagen at sutures that run from the lens center to anterior and posterior poles. The data that supports the findings of the reported studies are within the paper. Combining both PBS solutions together results in the formation of a white turbid solution. While the need for this high lipid content is unclear, disturbances of cholesterol homeostasis can lead to cataract formation. Scientists caution that more research is needed before deeming the drops as a safe and effective treatment for cataracts in humans. As shown in Fig. Failure of Oxysterols Such as Lanosterol to Restore Lens Clarity from Cataracts. Exp Eye Res. 101, 412413 (1986). The protective lens antioxidant defenses and the molecular chaperone reserve of -crystallin decrease with age so that the aging lens can no longer adequately protect itself from post-translational modifications of lens proteins. No suitable binding pose for lanosterol was identified. 30, 379381 (1994). Cataract Symptoms and Natural Cataract Treatments J Mol Biol. 7, 353368 (2015). Seo, S., Tonda, K., Uomori, A., Takeda, K. & Hirata, M. Effect of sterol biosynthesis inhibitor, SSF-109, on cholesterol synthesis in isolated rat hepatocytes. It is not surprising that the narrowed ATP binding pocket (Fig. PubMed Erie, J. C., Pueringer, M. R., Brue, S. M., Chamberlain, A. M. & Hodge, D. O. Statin Use and Incident Cataract Surgery: A Case-Control Study. Could eye drops be an alternative treatment to cataract surgery? Lanosterol is an amphipathic molecule enriched in the lens. Invest Ophthalmol Vis Sci. However, the failure of both oxysterols to solubilize lens protein homogenates suggesting that studies establishing oxysterol penetration into lens fibers may be moot. We also explore if eitheroxysterols adequately bind to B-crystallin chaperones at the molecular level. Rev Med Suisse. Therefore, altered cholesterol homeostasis may lead to cataract formation despite an increase in lanosterol. One of these, known as lanosterol, was shown to reverse cataracts in a July paper in Nature, but because lanosterol has limited solubility, the group who published that study had to inject the compound into the eye for it to exert its effects. (3) 0.25mM 25-hydroxycholesterol +2.0mg/mL B- crystallin. The finding, published on Nature, identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment. 366, 12191233 (2011). Davis G. The Evolution of Cataract Surgery. J Phys Chem Lett. Cataracts can develop if the proteins become disrupted, clump together, and break down, which is common with advancing age. These biochemical insults all lead to similar protein destabilization, the presence of partially unfolded aggregation-prone intermediates, and the formation of insoluble, light-scattering protein aggregates that appear as lens opacities13. Advances in pharmacotherapy of cataracts - PMC - National Center for Such a scenario may result in a poor binding environment for both lanosterol and 25-hydroxycholesterol. Behar-Cohen, F. & Wolfensberger, T. J. Ophthalmolgy: whats new in 2015?. The images or other third party material in this article are included in the articles Creative Commons license, unless indicated otherwise in a credit line to the material. New research may revolutionize cataract treatment With this blog, we'll be sharing the views of Dr. Kondrot Incubation for an additional 48hours in the lanosterol liposome media resulted in an apparent penetration of the amber liposomes into the lenses as noted by the slight color changes, especially around the nucleus as all treated lenses progressed to the mature nuclear cataract stage. The first synthetic cholesterol lowering drug associated with irreversible cataract formation was triparanol (MER-29)52. 5. Cataracts Melt Away Thanks To New Eye Drops Containing Steroid Lanosterol Popjak, G., Meenan, A., Parish, E. J. Lanosterol Benefits in 2018; Can Cataracts be Reversed using Lanosterol? A Noninvasive Alternative to Cataract Surgery? prepared images for publication. 2) taken after incubation were standardized to the same contrast and exposure, and by adjusting the pixel densities of each outer grid line to a standard value. MOE ribbon structures depicting the best docked complexes for lanosterol and 25-hydroxycholesterol with the wildtype and mutant B-crystallins. n=3S.D. If the aggregated proteins were solubilized, then the levels of proteins in the insoluble fractions should have been lowered in the 25-hydroxycholesterol treated lenses. 274, 558562 (1978). Exp Eye Res. Change in soluble/insoluble protein levels of 60-year-old human lens homogenate after 3 days incubation at 37C in media containing either 0.0, 0.25 or 0.50mM of 25-hydroxycholesterol. While the control lenses appear relatively clear after 48-hour exposure to lanosterol, the presence of lanosterol did not halt the further progression of cataracts. 8, when 25-hydroxycholesterol is placed in a solution of PBS, it remains as a precipitate and fails to dissolve into the solution. Clinical detection of precataractous lens protein changes using dynamic light scattering. Meehan, S. et al. 28, 462469 (1979). Exp Eye Res. Open Journal of Clinical and Medical Case Reports. CAS Arch Biochem Biophys. 8, 15137 (2017). Biswas, A. Google Scholar. Note that neither oxysterol could enter the dimer interface in the 2Y1Z mutant and the only interaction was perpendicular to the interface pocket. Additional protein-ligand interaction in our studies further disclosed the underlying cause for the poor binding of oxysterols, such as lanosterol, to the current B-crystallins models. There is no change in the levels of proteins in the soluble and insoluble fractions with or without the presence of lanosterol. The intact lens from each eye was removed by careful dissection from a posterior approach and cultured as previously described in sterile TC-199 bicarbonate media containing 30mM fructose and 20U/mL of penicillin-streptomycin in a humidified incubator under an atmosphere of 95% air and 5% CO2 at 37C36,37,38. There's a lot talk around which eye drop is perfect for our eyes. These results are in agreement with those of Shanmugam et al.30 in which the authors also failed to show any change in soluble protein levels in 40 nuclear cataracts cultured with lanosterol. C-KAD Two human lenses from a 47-year-old donor were cut through the center of the lens into four equal quadrants and weighed. These children shared a genetic mutation that blocked lanosterol production. Surgery is the only established treatment of cataracts and no anti-cataract drugs are available thus far. The percentage of protein in soluble and insoluble fractions were estimated separately for all samples in each group and averaged. Datiles, M. B. Most commonly used for dogs but can help cats, horses, and rabbits too. The protein content of the soluble protein in the supernatant was determined using the Bio-Rad Protein Assay (Hercules, CA). Crystal structures of alpha-crystallin domain dimers of alphaB-crystallin and Hsp20. 2, trauma-induced cataracts appeared as localized opacities that varied because of the levels of blunt physical trauma applied, while the ouabain-treated lenses developed cortical opacities and the osmotic inducer produced dramatic refractive index changes associated with significant lens swelling. Kador, P. F., Webb, T. R., Bras, D., Ketring, K. & Wyman, M. Topical KINOSTATTM ameliorates the clinical development and progression of cataracts in dogs with diabetes mellitus. Failure of Oxysterols Such as Lanosterol to Restore Lens - Nature These culture studies require carefully excised lenses that are cultured in specially buffered and osmotically compensated culture media at 37C in order to maintain their viability and clarity59,60. To evaluate this possibility, two lenses from a 47-year-old human were equally divided into 4 pie shaped portions and incubated in the dark for 3 days at 37C in media containing 0.2mM lanosterol dissolved in 10% ethanol. National Eye Institute CC BY-NC-ND 2.0. Interestingly, their parents lacked this mutation and never developed cataracts. While overall the docking scores from the MOE dock program appeared to overestimate binding compared to the Glide dock program, feasible binding with ATP was observed by both programs. 23, 4045 (2016). This paradigm that vision can only be restored through cataract surgery has recently been challenged by Zhao et al.23 and Makley et al.24 who report that interaction of lanosterol or 25-hydroxycholesterol with -crystallin chaperones enhance the ability of these chaperones to restore lens clarity by increasing their ability to physically dissolve protein aggregates and/or the denatured amyloid-like fibril proteins present in cataractous lenses. This hydrogen-bond was absent in the 2KLR and 2Y1Z models (Fig. Cholesterol derivatives, in addition to interacting with crystallins, also play an integral role in the regulation of cholesterol-dependent processes in fiber cell plasma membranes and in the maintenance of fiber cell membrane homeostasis50. Masayuki Mori. According to the World Health Organization, cataracts are the leading cause of blindness among people older than 55. The structures (Fig. It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a cholesterol synthesis pathway. p>0.5 ANOVA single factor analysis and n=4S.D. Philos Trans R Soc Lond B Biol Sci. Scientists surmised that lanosterol functions to keep the human lens clear by stopping the breakdown and clumping of the normally clear proteins in the lens. Biochim Biophys Acta. Kirby, T. J. Cataracts produced by triparanol. Chemerovski-Glikman, M. et al. Correspondence to [9] 123, 916917 (2017). Cataracts are usually treated with cataract surgery. For example, the Kd for lanosterol and 25-hydroxycholesterol, respectively, are predicted to be 653M and 11M against wt 2WJ7 (Table1, MOE dock), and 3.55mM and 579M (Table2, Glide dock). 51, 24732488 (2010). Daszynski DM, Santhoshkumar P, Phadte AS, et al. Ortwerth, B. J., Olesen, P. R. & Sharma, K. K. Solubilization of the lens water-insoluble fraction by sonication. N=3S.D. Zhao, L. et al. Ikesugi, K., Yamamoto, R., Mulhern, M. L. & Shinohara, T. Role of the unfolded protein response (UPR) in cataract formation. Could the oxysterol binding perhaps occur at the ATP binding site? Three technologies1 now in use and 2 in developmentmay go a long way toward transforming the field, whether by reducing the need for postoperative drops, revolutionizing the approach to intraocular lens (IOL) adjustment, or allowing the clinician to circumvent cataract surgery altogether. Wormstone, I. M., Collison, D. J., Hansom, S. P. & Duncan, G. A focus on the human lens in vitro. Adequate ATP binding onto the dimer interface of the 2WJ7 model was also observed, however, the binding of ATP to the interface of the mutant 2Y1Z was much weaker, suggesting that ATP would preferentially bind to the ATP pocket rather than the dimer interface. Lens fibre cell differentiation and organelle loss: many paths lead to clarity. Mol Vis. Results showed that 85% of the rabbits experienced a significant lessening of the severity of their cataracts. When used properly, castor oil eye drops might indirectly help reduce cataract symptoms by improving function in other parts of the eye in the following ways: Relieving dry eyes caused by allergies, infections and natural dryness Increasing blood circulation in the eye Helping maintain tear film Aiding in meibomian gland function A. To clarify these contrasting findings, we pursued a series of studies to evaluate whether oxysterols such as lanosterol or 25-hydroxycholesterol can reverse experimentally induced cataracts or to re-dissolve aggregated lens crystallin proteins. The Health Consequences of Smoking: A Report of the Surgeon General. Amazon.com : NOVEHA Cataract Drops for Pets | Advanced Lanosterol https://doi.org/10.1038/s41598-019-44676-4, DOI: https://doi.org/10.1038/s41598-019-44676-4. Therapeutic Pet Eye Drops for Cataract | Promotes Vision Health & Dryness Relief. . Dr. Kondrot Answers: Which eye drop is better DMSO or Oclumed? 6) is unable to accommodate the large oxysterol molecules. This treatment decreased preformed protein aggregates and also improved lens transparency. Lanosterol eye drops has been always associated with the reversal of chronic eye disorder; Cataracts. Plush Paws Products Advanced Lanosterol Solution + NAC | Dog Eye Care | Therapeutic Pet Eye Lubricating Drops for Cataracts | Promotes Vision Health & Dryness Relief in Pets (10 Milliliters) 421 $5899 ($58.99/Count) $53.09 with Subscribe & Save discount FREE delivery Wed, Jun 28 Or fastest delivery Tue, Jun 27 Small Business Science. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Kuszak, J. R., Zoltoski, R. K. & Tiedemann, C. E. Development of lens sutures. The lens grows throughout life with new fiber cells continually laid on top of the older fiber cells so that the fiber cell depth within the lens is directly related to the age and stage of lens development2,3,4. Google Scholar. Moran, S. D., Zhang, T. O., Decatur, S. M. & Zanni, M. T. Amyloid fiber formation in human gammaD-Crystallin induced by UV-B photodamage. ULC, 1010 Sherbooke St West, Suite #910, Montreal, QC, Canada, H3A 2R7, 201. Two binding pockets were defined for the docking studies.