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Kota V. Ramana, Nilesh M. Kalariya, Mohammad Shoeb, Naseem H. Ansari, Satish K. Srivastava; Prevention Of Endotoxin-induced Uveitis By Anti-diabetic Drug Metformin In Rats. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5486.
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Metformin is a commonly used anti-diabetic drug in patients because of its well established efficacy and negligible side effects. Its efficacy in preventing ocular inflammatory diseases is not known. Hence, we investigated anti-ocular inflammatory effects of Metformin in endotoxin-induced uveitis (EIU) in rats.
EIU was induced by subcutaneous injection of lipopolysaccharide (LPS) (150 ug) in Lewis rats treated with or without metformin. The number of infiltrating cells and levels of proteins were determined in the aqueous humor (AqH). The MILLIPLEX MAG Rat cytokine/chemokine magnetic bead array was used to determine the levels of various cytokines and chemokines in AqH. Human primary non-pigment ciliary epithelial cells (HNPECs) were used to determine anti-inflammatory efficacy in vitro.
Compared to controls, the EIU rat eyes AqH had significantly higher number of infiltrating cells, total protein, and various cytokines and chemokines (TNF-α, MCP-1, IL-1β, MIP-1α, IL-6, Leptin, IL-18, and GRO/KC) and metformin significantly prevented these alterations. Metformin also prevented the expression of Cox-2 and activation of NF- B, and increased the activation of AMPK in the ciliary bodies and retinal tissues. Moreover, metformin also prevented the expression of Cox-2, iNOS, and phosphorylation of NF- B in HNPECs and decreased the levels of Nitrate/Nitrite and PGE2 in cell culture media.
Our results for the first time demonstrate a novel role of anti-diabetic drug, metformin, in suppressing uveitis in rats and suggest that it could be developed as a potential agent to prevent uveitis complications.
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