Non-infected C57BL/6 and C57BL/6 CXCL102/2 mice injected with normal RBC served as control groups

cumulation of subretinal deposits between RPE and Bruch’s membrane and RPE morphologic changes. Dysregulated growth factor expression, scavenger receptors, and the mTOR pathway have all been implicated in mediating or modulating these pathologic changes. Redox of RPE also plays a critical role in combating oxidative stress. Among the cellular antioxidant constituents, reduced glutathione is the major non-protein thiol antioxidant with pluripotent functions. Even though GSH is synthesized in the cytosol, it is distributed in intracellular organelles such as endoplasmic reticulum, nucleus and mitochondria. GSH depletion has been attributed to apoptosis either by predisposing cells to apoptosis or by modulating mitochondrial membrane potential and subsequent activation of caspases. Since mitochondrial GSH plays a significant role in cellular defense against pro-oxidants, depletion of mGSH poses a threat to cell viability. Elucidating GSH transport mechanisms of different cellular compartments has received SB-366791 considerable recent attention. In the brain, release of GSH from astrocytes is an important component of GSH homeostasis. Brain astrocytes maintain redox balance by the ATP-dependent extrusion of GSH by ATP-binding cassette 24220009 transporter, multidrug resistance protein 1 . Studies have demonstrated that both glutathione disulfide and GSH are substrates for MRP1. However, information on expression and regulation of proteins associated with GSH efflux in the retina is scarce. Differences in mRNA expression of MRPs in different RPE cell lines was reported. However, the role of efflux transporters, particularly MRP1 in GSH regulation in RPE cells under unstressed and stressed conditions has not been studied so far. MRP1-Mediated GSH Efflux in RPE Cells a-Crystallins have been found in many non-lenticular tissues including the retina. aA and aB crystallin both serve a cell protection function and a chaperone function. In lens epithelial cells, a-crystallins are anti-apoptotic against UVA-irradiation and tumor necrosis factor-a stimulation. a-Crystallins also function as chaperones by preventing aggregation and pathologic protein misfolding. Overexpression of either human HSP27 or aB crystallin resulted in increased total GSH levels and decreased basal levels of intracellular reactive oxygen species . Our laboratory has investigated the role of a-crystallins in RPE cell physiology and their regulation by oxidative stress. Lack of a-crystallins rendered RPE cells more susceptible to apoptosis caused by oxidative stress. Overexpression of aA or aB crystallin had similar degrees of protection in lenticular as well as non-lenticular cells. We showed that RPE cells lacking either aA or aB crystallin are equally susceptible to H2O2induced oxidant insult. Recently, we discovered that aB crystallin is secreted from RPE 8199874 cells in exosomes, and exogenous aB crystallin protected RPE cells from oxidative stress-induced apoptosis. The link between the protective function of a-crystallin and cellular antioxidant status is not well understood. Both GSH and redoxins are major factors with critical redox functions in RPE cells. GSH levels are elevated in a-crystallin overexpressing human lens epithelial cells. However, the nature and mechanism of GSH participation in the a-crystallin-mediated antiapoptotic function of RPE cells has not been studied. Here, we investigated the relationship between GSH, redoxins and the antiapoptotic function of a- crystallins in RPE.