Role Of Retinal Pigment Epithelium In Retinal Disorders

National Eye Institute

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Abstract

Retinal pigment epithelium (RPE), a single layer of cells present between the retina and choroid in the eye, is vital for the normal functioning of the retina. Many of the inflammatory, infectious and hereditary diseases of the retina are associated with the degeneration and /or dysfunction of the RPE. We have developed human RPE cell culture system and have used this as a model to investigate the various roles of RPE in the pathophysiology of retinal disorders. We have focussed our attention on Transforming Growth factor-beta (TGF-b), since TGF-b is involved in retinal disorders of proliferative, inflammatory and infectious etiology. Retinochoroiditis induced by Toxoplasma gondii (T. gondii ), a protozoan parasite, infections results in inflammation and necrosis of the retina, and is one of the common causes of uveitis. When T. gondii infects RPE cells in vitro, we observed an elevated mRNA and protein secretion of TGF-b, a native anti-inflammatory agent. These results indicate interactions between host retinal cells and T. gondii that may play an active role in the pathogenesis of retinochoroiditis. Choroidal neovascularization (CNV) is one of the major events in the age related macular degeneration (ARMD), a leading cause of visual impairment in the aged population. Elevated expression of TGF-b in vitreous, retina and RPE has been closely correlated with the retinal fibrosis and choroidal neovascularization. Since vascular endothelial growth factor (VEGF) is associated with CNV, we have examined the role of RPE in VEGF expression. TGF-b is found to be the potent inducer of VEGF secretion. RT-PCR analyses indicated the presence of 121,165 and 189 aa isoforms of VEGF, which are up regulated by TGF-b. By using specific inhibitors of mitogen activated protein kinases, we found that TGF-b appears to transcriptionally activate VEGF through MAPK and smad pathway. Regulation of the expression of VEGF by TGF-b strongly suggests an important role for TGF-b in CNV in ARMD.