Project: Research project

Project Details


The long range goal of this proposal is to determine the cause of the retinal degeneration in a newly described mouse model C57vit/vit. Photoreceptor cell nuclei are slowly lost over the course of a year in this animal model and the retinal pigment epithelium (RPE) is unevenly pigmented. The involvement of these two cell types and the protracted nature of the degeneration make the C57vit/vit a very promising model for human Retinitis Pigmentosa. Our preliminary data indicate that levels of the retinoids retinyl palmitate, 11-cis retinaldehyde and all-trans retinaldehyde are elevated at 6 weeks in the eyes of C57vit/vit mice; rhodopsin levels are significantly lower than controls by 12 weeks. In normal retinas, photoreceptors and RPE function cooperatively to regulate retinoids used in the visual cycle for the synthesis of rhodopsin. The proposed work will determine by HPLC whether the accumulation of retinoids is in photoreceptors or RPE. The functions of these two cell types will be evaluated to determine the site of the primary defect. Photoreceptor cell function will be assessed by morphometric studies of ROS turnover; spectrophotometric studies of rhodopsin levels; in vitro incubation studies of the synthesis and post-translational modifications of rhodopsin; and thin-layer chromatographic studies of phospholipid synthesis. RPE function will be assessed by morphometric analysis of the extent of pigmentation; and by determining the ability to phagocytize shed ROS discs by counting phagosomes in fixed retinal tissue obtained shortly after peak disc shedding. The morphological and biochemical data to be compiled from the proposed studies will guide development of intervention strategies and will serve as a yardstick against which their efficacy can be evaluated.
Effective start/end date9/30/929/29/99


  • National Eye Institute


  • Medicine(all)


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