Project Details
Description
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.
Status | Finished |
---|---|
Effective start/end date | 9/30/92 → 9/29/99 |
Funding
- National Eye Institute
ASJC
- Medicine(all)
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