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. In rat, 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. The gene for PDGFD in mouse has been knocked out. No major defects in early development are apparent but an age-related phenotype in under investigation. 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 terminal differentiation.A knock out model of lengsin is now being evaluated as another model for age-related defects in ocular function. 3: Retbindin is a novel protein of the retina. Using in situ hybridization and laser capture dissection we have shown that retbindin is essentially specific for photoreceptors where it is a candidate for binding and transport of pigment molecules. Preliminary results in transgenic mice suggest a possible role photoreceptor gene expression. 4: AMD and complement factor H (CFH). Common sequence variants of CFH have major roles in determining susceptibility to 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. Work is in progress to develop an assay to investigate drugs that could modulate this binding activity.
