Related Experiment Video
Updated: May 22, 2026
Experimental Autoimmune Uveitis: An Intraocular Inflammatory Mouse Model
Published on: January 12, 2022
Antidiabetic drug metformin suppresses endotoxin-induced uveitis in rats
Nilesh M Kalariya1, Mohammad Shoeb, Naseem H Ansari
1Department of Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Purpose:
To investigate the therapeutic effects of metformin, a commonly used antidiabetic drug, in preventing endotoxin-induced uveitis (EIU) in rats.
Methods:
EIU in Lewis rats was developed by subcutaneous injection of lipopolysaccharide (LPS; 150 microg). Metformin (300 mg/kg body weight, intraperitoneally) or its carrier was injected either 12 hours before or 2 hours after LPS induction. Three and 24 hours after EIU, eyes were enucleated and aqueous humor (AqH) was collected. The MILLIPLEX-MAG Rat cytokine-chemokine magnetic bead array was used to determine inflammatory cytokines. The expression of Cox-2, phosphorylation of AMPK, and NF-κB (p65) were determined immunohistochemically. Primary human nonpigmented ciliary epithelial cells (HNPECs) were used to determine the in vitro efficacy of metformin.
Results:
Compared with controls, the EIU rat AqH had significantly increased number of infiltrating cells and increased levels of various cytokines and chemokines (TNF-α, MCP-1, IL-1β, MIP-1α, IL-6, Leptin, and IL-18) and metformin significantly prevented the increase. Metformin also prevented the expression of Cox-2 and phosphorylation of p65, and increased the activation of AMPK in the ciliary bodies and retinal tissues. Moreover, metformin prevented the expression of Cox-2, iNOS, and activation of NF-kB in the HNPECs and decreased the levels of NO and PGE2 in cell culture media.
Conclusions:
Our results for the first time demonstrate a novel role of the antidiabetic drug, metformin, in suppressing uveitis in rats and suggest that this drug could be developed to prevent uveitis complications.
Insights
Metformin, an antidiabetic drug, effectively prevents endotoxin-induced uveitis (EIU) in rats by reducing inflammation. This study suggests metformin
Area of Science:
- Ophthalmology
- Pharmacology
- Immunology
Background:
- Endotoxin-induced uveitis (EIU) is an inflammatory eye condition.
- Metformin is a widely used antidiabetic medication.
Purpose of the Study:
- To investigate the therapeutic potential of metformin in preventing EIU in a rat model.
- To explore metformin's effects on inflammatory markers and cellular pathways involved in uveitis.
Main Methods:
- EIU was induced in Lewis rats using lipopolysaccharide (LPS).
- Metformin was administered before or after LPS induction.
- Inflammatory cytokines, Cox-2, AMPK, NF-κB, nitric oxide (NO), and prostaglandin E2 (PGE2) were analyzed in vivo and in vitro.
Main Results:
- Metformin significantly reduced inflammatory cell infiltration and key cytokines (TNF-α, IL-1β, IL-6) in rat aqueous humor.
- Metformin suppressed Cox-2 expression and NF-κB activation while enhancing AMPK activation in ocular tissues.
- In vitro, metformin inhibited Cox-2, iNOS, NF-κB activation, and reduced NO and PGE2 levels in human ciliary epithelial cells.
Conclusions:
- Metformin demonstrates significant anti-inflammatory and protective effects against EIU in rats.
- These findings highlight a novel therapeutic role for metformin in managing uveitis and its complications.
