1: Platelet-derived growth factor D (PDGFD) belongs to the PDGF/VEGF family. PDGFD has a key role in control of lens growth and anti-PDGFD strongly inhibits lens epithelial cell proliferation This finding suggests a major in vivo role for PDGFD in the mechanisms of coordinated growth of eye tissues. PDGFD is also expressed in photoreceptors with striking localization in the synaptic ends. A functional promoter of the PDGFD gene has been identified and correctly directs expression of a GFP reporter to eye tissues. A conditional knock out of PDGFD in mouse is nearing completion. ? 2: Lengsin is a novel member of the glutamine synthetase (GS) superfamily that is specific for the vertebrate eye lens. Lengsin is expressed specifically in the layer of terminally differentiating secondary fiber cells in which nuclei and other organelles are lost and cytoskeleton and intracellular junctions are reorganized. Y2H experiments suggest that lengsin has a role as a chaperone of major cytoskeletal components of the lens and participates in the reorganization of cellular components in terminla differentiation.A knock out model of lengsin is now completed and is being examined.? 3: Complement factor H (CFH) has an important role in the development of age-related macular degeneration (AMD). Using yeast 2-hybrid libraries for aged human RPE/choroid and retina and bait constructs for the AMD-related domain 7 of CFH we have identified potentially important targets for CFH binding in human RPE/choroid. These results have been confirmed by immunofluorescence localization and have implications for intervention in the progression of AMD.? 4: Retbindin is a novel protein of the retina. We created transgenic mice to overexpress human retbindin. These have been analyzed using custom cDNA microarrays. Results suggest that retbindin may have a role in photoreceptor function and activity.

National Institute of Health (NIH)
National Eye Institute (NEI)
Intramural Research (Z01)
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U.S. National Eye Institute
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Wyatt, Keith; Gao, Chun; Tsai, Jen-Yue et al. (2008) A role for lengsin, a recruited enzyme, in terminal differentiation in the vertebrate lens. J Biol Chem 283:6607-15
Harding, Rachel L; Howley, Sinead; Baker, Lee J et al. (2008) Lengsin expression and function during zebrafish lens formation. Exp Eye Res 86:807-18
Wyatt, Keith; White, Helen E; Wang, Luchun et al. (2006) Lengsin is a survivor of an ancient family of class I glutamine synthetases re-engineered by evolution for a role in the vertebrate lens. Structure 14:1823-34
Wistow, Graeme (2006) The NEIBank project for ocular genomics: data-mining gene expression in human and rodent eye tissues. Prog Retin Eye Res 25:43-77
Ray, Sugata; Gao, Chun; Wyatt, Keith et al. (2005) Platelet-derived growth factor D, tissue-specific expression in the eye, and a key role in control of lens epithelial cell proliferation. J Biol Chem 280:8494-502