Studies on the physicochemical characteristics of a fatty acid-binding site on the interphotoreceptor retinoid-binding protein (IRBP) with fluorescent fatty acid analogs demonstrated that fatty acids were bound in a hydrophobic environment, that there was a single, specific fatty acid-binding site for each molecule of IRBP, and that there was nonradiative energy transfer from tryptophan residues to bound ligand. Probing the microenvironment of bound fluorophore with a quencher indicated a highly structured binding site. Studies of the formation and release of 11-cis retinal by the retinal pigment epithelium at a physiological concentration of IRBP demonstrated that a sequential (ie, unbranched) pathway mediates the processing of all-trans retinol to 11-cis retinal and its transfer to IRBP. In the mivitmivit mutant mouse model of retinal degeneration, retinyl palmitate was evaluated fourfold and IRBP was elevated twofold in the eyes of affected mice, as compared with that in controls at 6-8 weeks of postnatal development. At the same time, IRBP mRNA was not elevated. The elevation in retinyl palmitate may be a significant factor in the retinal degeneration in this mutant, and IRBP turnover may be affected by an aberration in retinoid metabolism. A 72 kDa heat shock protein (hsp) which bound specifically to peptide 1169-1191, a potent uveitogenic determinant of IRBP, has been identified in Lewis rat B cells and Epstein Barr Virus-transformed B cells from normal human donors and uveitis patients. This hsp has a potential role in antigen processing and presentation by antigen-presenting cells.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000070-16
Application #
3777603
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
1993
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Cortes, Lizette M; Mattapallil, Mary J; Silver, Phyllis B et al. (2008) Repertoire analysis and new pathogenic epitopes of IRBP in C57BL/6 (H-2b) and B10.RIII (H-2r) mice. Invest Ophthalmol Vis Sci 49:1946-56
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Tsina, Efthymia; Chen, Chunhe; Koutalos, Yiannis et al. (2004) Physiological and microfluorometric studies of reduction and clearance of retinal in bleached rod photoreceptors. J Gen Physiol 124:429-43
Chen, Shanyi; Samuel, William; Fariss, Robert N et al. (2003) Differentiation of human retinal pigment epithelial cells into neuronal phenotype by N-(4-hydroxyphenyl)retinamide. J Neurochem 84:972-81
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