The overall objective of the application is the evaluation of the role of oxidative stress in the development of human senile cataract. The application will study formation of nuclear cataract in a guinea pig model for nuclear cataract formation in aging humans. The guinea pig forms a nuclear cataract in response to hyperbaric oxygen. Traditional techniques such as Raman spectroscopy and 2-dimensional gel electrophoresis, SDS PAGE and immunoblot analyses will be combined with more innovative methods such as LC assays for disulfide bonds pioneered for lens proteins by Dr. M. Lou, a collaborator. The analyses will provide information on the relative contribution of membrane-associated aggregation and soluble crystallin aggregation to opacification in nuclear cataract of the hyperbaric oxygen/guinea pig model. While elements of the application such as the studies with knockout and transgenic animals may be premature, the application is generally very strong and important new information on cataract formation can be expected.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-VISC (01))
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Liberman, Ellen S
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Oakland University
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Cencer, Caroline S; Chintala, Shravan K; Townsend, Tenira J et al. (2018) PARP-1/PAR Activity in Cultured Human Lens Epithelial Cells Exposed to Two Levels of UVB Light. Photochem Photobiol 94:126-138
Raju, Murugesan; Mooney, Brian P; Thakkar, Kavi M et al. (2015) Role of ?A-crystallin-derived ?A66-80 peptide in guinea pig lens crystallin aggregation and insolubilization. Exp Eye Res 132:151-60
Padgaonkar, Vanita A; Leverenz, Victor R; Bhat, Aparna V et al. (2015) Thioredoxin reductase activity may be more important than GSH level in protecting human lens epithelial cells against UVA light. Photochem Photobiol 91:387-96
Lyons, Brian; Karuso, Peter; Jamie, Joanne F et al. (2014) Characterisation of a novel UV filter in the lens of the thirteen-lined ground squirrel (Ictidomys tridecemlineatus). Exp Eye Res 121:114-20
Giblin, Frank J; David, Larry L; Wilmarth, Phillip A et al. (2013) Shotgun proteomic analysis of S-thiolation sites of guinea pig lens nuclear crystallins following oxidative stress in vivo. Mol Vis 19:267-80
Giblin, Frank J; Lin, Li-Ren; Simpanya, Mukoma F et al. (2012) A Class I UV-blocking (senofilcon A) soft contact lens prevents UVA-induced yellow fluorescence and NADH loss in the rabbit lens nucleus in vivo. Exp Eye Res 102:17-27
Goldenberg, David T; Giblin, Frank J; Cheng, Mei et al. (2011) Posterior vitreous detachment with microplasmin alters the retinal penetration of intravitreal bevacizumab (Avastin) in rabbit eyes. Retina 31:393-400
Giblin, Frank J; Lin, Li-Ren; Leverenz, Victor R et al. (2011) A class I (Senofilcon A) soft contact lens prevents UVB-induced ocular effects, including cataract, in the rabbit in vivo. Invest Ophthalmol Vis Sci 52:3667-75
Simpanya, Mukoma F; Leverenz, Victor R; Giblin, Frank J (2010) Expression and purification of his-tagged recombinant mouse zeta-crystallin. Protein Expr Purif 69:147-52
Giblin, F J; Quiram, P A; Leverenz, V R et al. (2009) Enzyme-induced posterior vitreous detachment in the rat produces increased lens nuclear pO2 levels. Exp Eye Res 88:286-92

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