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 other diseases of the retina are associated with the degeneration and /or dysfunction of the RPE. We have developed a 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 focused our attention on transforming Growth factor-beta (TGF-b), since TGF-b is involved in retinal disorders of proliferative, inflammatory and infectious etiology. Retinal and Choroidal neovascularization (CNV), observed during age related macular degeneration (ARMD) and proliferative vitreoretinopathy (PVR) associated with retinal detachments, are the leading causes of visual impairment. Elevated expression of TGF-b in vitreous, retina and RPE has been closely correlated with the retinal fibrosis and CNV. However, the sources and production of TGF-b by retinal resident cells were not clearly known. We have examined the role of various cytokines and other mediators in the regulation of the expression of TGF-b by RPE. Our results demonstrated a differential role for interferon (IFN)-g, which enhanced TGF-b1 but inhibited TGF-b2 production. Interestingly, other inflammatory mediators such as tumor necrosis factor (TNF)-alpha and interleukin-1 enhanced the secretion of both TGF-b1 and TGF-b2. These observations were corroborated by mRNA analyses by Real-time and conventional RT-PCR methods. The contrasting effects of IFN-g on TGF-b1 and TGF-b2 sheds new light on the possible differential actions of TGF-b1 and TGF-b2 in the pathophysiology of retinal diseases. Further studies are in progress to evaluate the potential role of TGF-b1 and TGF-b2 and their receptors in the retinal diseases. We are evaluating the role and expression of Interferon-beta, which plays a vital role as an antiviral, anti-inflammatory agent, in the retinal and choroidal diseases. There is increasing evidence that Interferon-beta prevents blood-tissue barrier by preserving vascular cell functions. In human choroidal fibroblast cells (HCHF), IFN-gamma induced secretion of IFN-beta, which was enhanced significantly by the synergistic action of TNF-alpha. Human RPE cells did not secrete IFN-beta by IFN-gamma and TNF-alpha treatment. Interleukins and growth factors had no effects on IFN-beta production by both HCHF and RPE cells. Real-time and conventional RT-PCR methods showed enhanced expression of IFN-beta mRNA in IFN-gamma and TNF-alpha treated HCHF. IFN-beta produced by choroidal cells may act to protect the integrity of the choroidal vasculature and blood-retinal barrier during inflammatory conditions.

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National Eye Institute (NEI)
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U.S. National Eye Institute
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Nagineni, Chandrasekharam N; William, Abitha; Cherukuri, Aswini et al. (2016) Inflammatory cytokines regulate secretion of VEGF and chemokines by human conjunctival fibroblasts: Role in dysfunctional tear syndrome. Cytokine 78:16-9
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