When the retina is separated (detached) from the overlying monolayer of retinal pigment epithelium (APE) experimentally or as a consequence of injury, degenerative and proliferative changes occur in specific retinal cell types. When the retina is reapposed (reattached) to the RPE surface, the photoreceptor-RPE interface undergoes a significant degree of cellular """"""""remodeling"""""""". In these experiments the detachment/ reattachment model will be used in a range of investigations designed to enhance our understanding of the retina's cellular response to, and recovery from, injury. 1. The relationship between photoreceptor outer segment degeneration, regeneration, and the integrity of the interphotoreceptor matrix (IPM) will be studied using the experimental retinal detachment model. A combination of immunochemical and lectin cytochemical techniques will be used to assess changes in specific [PM domains and components, and their relationship to retinal recovery. 2. Members of the Integrin family of adhesion receptors mediate the attachment of cells to extracellular matrix molecules. Integrins have been implicated in RPE cell anchorage to Bruch's membrane, in retina-APE adhesion, and in vitreoretinal adherence. A.) Specific integrins will be identified at three key retinal locations: the photoreceptor-RPE interface, Bruch's membrane, and the vitreoretinal border. B.) Integrins expressed by RPE cells in vivo will be compared to those expressed by RPE cells at various stages of differentiation in vitro. C.) Changes in integrin types and levels of expression will be compared in the normal, detached, and reattached retinas. 3. Transforming growth factor-beta (TGF-B) and fibroblast growth factors (FGF) are known to be present in the retina, however their functions are unknown. We will examine the roles of these two factors in the context of experimental retinal detachment/reattachment. We will identify: A.) Cellular and extracellular sites within the normal retina where these factors are located; B.) Modifications in their levels and/or distributions in the detached and reattached retina; C.) The retinal cell types that have receptors for these molecules; and D.) The effect(s) of exogenous TGF-B on intraretinal proliferation and interphotoreceptor matrix biosynthesis in vivo.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Visual Sciences A Study Section (VISA)
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University of California Santa Barbara
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Santa Barbara
United States
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Ozaki, S; Radeke, M J; Anderson, D H (2000) Rapid upregulation of fibroblast growth factor receptor 1 (flg) by rat photoreceptor cells after injury. Invest Ophthalmol Vis Sci 41:568-79
Anderson, D H; Hageman, G S; Mullins, R F et al. (1999) Vitronectin gene expression in the adult human retina. Invest Ophthalmol Vis Sci 40:3305-15
Lewis, G P; Fisher, S K; Anderson, D H (1996) Fate of biotinylated basic fibroblast growth factor in the retina following intravitreal injection. Exp Eye Res 62:309-24
Geller, S F; Lewis, G P; Anderson, D H et al. (1995) Use of the MIB-1 antibody for detecting proliferating cells in the retina. Invest Ophthalmol Vis Sci 36:737-44
Lewis, G P; Guerin, C J; Anderson, D H et al. (1994) Rapid changes in the expression of glial cell proteins caused by experimental retinal detachment. Am J Ophthalmol 118:368-76
Pfeffer, B A; Flanders, K C; Guerin, C J et al. (1994) Transforming growth factor beta 2 is the predominant isoform in the neural retina, retinal pigment epithelium-choroid and vitreous of the monkey eye. Exp Eye Res 59:323-33
Guerin, C J; Lewis, G P; Fisher, S K et al. (1993) Recovery of photoreceptor outer segment length and analysis of membrane assembly rates in regenerating primate photoreceptor outer segments. Invest Ophthalmol Vis Sci 34:175-83
Lewis, G P; Erickson, P A; Guerin, C J et al. (1992) Basic fibroblast growth factor: a potential regulator of proliferation and intermediate filament expression in the retina. J Neurosci 12:3968-78
Lewis, G P; Erickson, P A; Anderson, D H et al. (1991) Opsin distribution and protein incorporation in photoreceptors after experimental retinal detachment. Exp Eye Res 53:629-40
Hageman, G S; Kirchoff-Rempe, M A; Lewis, G P et al. (1991) Sequestration of basic fibroblast growth factor in the primate retinal interphotoreceptor matrix. Proc Natl Acad Sci U S A 88:6706-10

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