ROLE OF RETINAL PIGMENT EPITHELIUM IN RETINAL DISORDERS

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Retinal pigment epithelium (RPE), a single layer of cells present between the retina and choroid, is vital for the normal functioning of the retina. Many of the retinal diseases are caused by the disfunction of RPE. Human RPE cell cultures (HRPE) were used as a model to investigate the various roles of RPE in the pathophysiology of retinal disorders. We reported that human RPE cells upregulate mRNA levels and secrete significant quantities of IL-6, ICAM-1, GMCSF, nitric oxide and vascular endothelial growth factor in response to the stimulation by inflammatory cytokines. Toxoplasma gondii,that frequently causes retinochoroiditis in ocular toxoplasmosis,infection of HRPE induces secretion of IL-1, IL- 6, GMCSF and ICAM-1 but not nitric oxide by transcriptional activation of their genes. The secretion of these molecules by HRPE suggests that RPE plays a critical role in the immuno- pathological processes of retinal disorders. Transforming growth factor-beta (TGF-b) is involved in retinal disorders of proliferative,inflammatory and infectious etiology. Expression of TGF-b in ocular tissues is altered in age related macular degeneration, diabetic retinopathy and proliferative vitreoretinopathy. We have used primary HRPE cultures to evaluate the role of inflammatory mediators and T.gondii infection on TGF-b secretion. HRPE cells secreted TGF-b1 in a latent form while 15-40 % of secreted TGF-b2 was in a mature (active) form. IL-1 and TNF-alpha stimulated secretion of TGF- b1 and b2. Interferon-gamma stimulated secretion of TGF-b1 but inhibited secretion of TGF-b2. T. gondii infection of HRPE cells as well as treatment of HRPE cells with soluble extracts of T.gondii induced secretion of TGF-b1 and TGF-b2. TGF-b mRNA levels under these conditions correlated with the levels of secreted TGF-b suggesting a possible transcriptional regulation. TGF-b secreted by HRPE cells in response to inflammatory cytokines and T. gondii infection may play an important role in the pathophysiological processes of inflammatory and infectious diseases of the retina. - Human retinal pigment epithelial cells, age related macular degeneration, diabetic retinopathy, inflammation, cytokines, toxoplasmosis.