Vitamin A And Ocular Tissues

National Eye Institute

Investigators

Linked publications & trials

Abstract

Retinoic acid is a natural derivative of vitamin A and has a profound effect on many cellular functions including cell growth, differentiation, and apoptosis. Its synthetic analogs also have significant effects on cellular function. Our studies on the effect on cultured retinal pigment epithelial(RPE) cells of N?(4?hydroxyphenyl)retinamide (4HPR, fenretinide), an amide analog of retinoic acid that exerts its chemotherapeutic effects on cancer cells through induction of apoptosis, demonstrated that fenretinide induces apoptosis in human RPE cells and that retinoic acid receptors regulate this apoptosis, the generation of reactive oxygen species and the expression of heme oxygenase-1 and Gadd 153.[unreadable] NORPEG (novel retinal pigment epithelial cell gene, RAI14) is a gene that we originally characterized from the human retinal pigment epithelial (RPE) cell line ARPE?19 and showed to be regulated by retinoic acid. Our research has now demonstrated cell density-dependent[unreadable] nuclear/cytoplasmic localization of NORPEG protein in ARPE-19 cells.[unreadable] Immunofluorescence analysis, done in collaboration with the laboratory of Sylvia Smith, of the expression of NORPEG protein in retinal Muller and ganglion cells and mouse retina demonstrated Norpeg expression in primary cultures of mouse Muller and Ganglion cells and in the cell of the ganglion cell layer, inner nuclear layer and RPE in the mouse retina. [unreadable] Interphotoreceptor retinoid?binding protein (IRBP) is a component of the interphotoreceptor matrix (IPM) and is known to bind visual cycle retinoids. Collaborative work done with the laboratory of M. Carter Cornwall examined the role of IRBP in a study of the dependence of retinol production and removal on photoproduct decay and cell morphology. [unreadable] Collaborative research done with the laboratory of Daniel Organisciak examined the effect of visible light on normal and transgenic rats and characterized a novel retinoic acid derivative in retinas of the P3H-3 rat, and animal model of human retinal degeneration.