Studies previously supported by this grant dealt with composition, mechanisms and significance of protein transport in photoreceptors and ganglion cells of the retina, in both health and disease. These studies will be extended in the next project period, with emphasis on human hereditary retinal diseases, retinoid-binding proteins, development of rat retinas, and novel bipolar cells in the retinas of humans and other mammals that are reactive for recoverin, a retina-specific calcium-binding protein.
The specific aims are: (1) To extend light and electron microscopic analysis of donor retinas from patients with different genetic forms of retinitis pigmentosa (RP) and other inherited retinal dystrophies, using immunocytochemistry to localize proteins that are specific to rods, cones, retinal pigment epithelium and Muller cells, and the interphotoreceptor matrix. This will reveal if RP retinas that still contain photoreceptors lack or show abnormal distribution of retina-specific proteins that may influence photoreceptor survival. (2) To provide new information on the roles played by different forms of vitamin A in development of the retina. Retinoid-binding proteins (cellular retinaldehyde- and retinoic acid-- binding proteins, interphotoreceptor retinoid-binding protein) will be localized in the retinas of developing rats by immunocytochemistry and cells responsible for their synthesis will be identified by in situ hybridization. (3) Retinoic acid acts as a morphogen and is thought to regulate pattern formation in other developing systems (limb bud, brain and spinal cord). We previously documented early, transitory expression of retinoic acid-binding protein in rat retinal neuroblasts, consistent with our hypothesis that retinoic acid is essential for normal development of the retina, a precisely patterned tissue. To test this, we will identify cells that have nuclear receptors for retinoic acid in retinas of adult and developing rats using immunocytochemistry and in situ hybridization. (4) To extend our studies of a population of bipolar cells that are reactive for recoverin in adult human and rat retinas. These cells will be characterized in detail in developing monkey and rat retinas by light and electron microscopic immunocytochemistry.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY001311-19
Application #
3255862
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1977-02-01
Project End
1997-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
19
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Lei, B; Bush, R A; Milam, A H et al. (2000) Human melanoma-associated retinopathy (MAR) antibodies alter the retinal ON-response of the monkey ERG in vivo. Invest Ophthalmol Vis Sci 41:262-6
Fariss, R N; Li, Z Y; Milam, A H (2000) Abnormalities in rod photoreceptors, amacrine cells, and horizontal cells in human retinas with retinitis pigmentosa. Am J Ophthalmol 129:215-23
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Gregory-Evans, K; Fariss, R N; Possin, D E et al. (1998) Abnormal cone synapses in human cone-rod dystrophy. Ophthalmology 105:2306-12
Milam, A H; Li, Z Y; Fariss, R N (1998) Histopathology of the human retina in retinitis pigmentosa. Prog Retin Eye Res 17:175-205
Fariss, R N; Apte, S S; Luthert, P J et al. (1998) Accumulation of tissue inhibitor of metalloproteinases-3 in human eyes with Sorsby's fundus dystrophy or retinitis pigmentosa. Br J Ophthalmol 82:1329-34

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