MEMBRANE BIOSYNTHESIS IN NORMAL AND DYSTROPHIC RETINAS

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DESCRIPTION (adapted from the applicant's abstract): The principal investigator seeks to link mutations that can induce retinal degeneration in humans with disordered rhodopsin biosynthesis/transport and photoreceptor cell death. Many human retinal degenerations involve mutant genes expressed only in rods, yet cones die. How the injury of rods leads to cone death is unclear. The specific aims of this application are to: (1) develop transgenic Xenopus laevis as a model system to determine factors that perturb rhodopsin synthesis and transport and (2) develop models of retinal degeneration in transgenic Xenopus laevis to permit assessment of the impact of the death of rods on cone survival. To accomplish this, the investigator will determine: (1) where the transgene products are localized within photoreceptor cells; (2) the effect of the transgene products on the biosynthesis and transport of outer segment membrane proteins; and (3) their impact on photoreceptor cell viability. Preliminary results have been obtained using the opsin promoter to drive expression of green fluorescent protein (GFP) and GFP fusion proteins. The transgene products are expressed only in the major rods and are detectable 5 days after fertilization in the eye of the living tadpole. Since the frog retina is cone-rich, these transgenic frogs are suitable for examining the interaction of dying rods and the neighboring cones as models of human retinitis pigmentosa.