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Kota V. Ramana, Umesh C. Yadav, Shoeb Mohammad, Satish K. Srivastava; Aldose Reductase Deficiency Protects From Uveitis Complications In Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4325.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate how aldose reductase (AR) mediates ocular inflammation in uveitis.
Autoimmune- and endotoxin-induced uveitis (EAU and EIU, respectively) were developed in ARKO and wild type (WT) mice. EAU was induced by immunizing mice with human interphotoreceptor retinoid-binding peptide (hIRPB-1-20) and EIU was induced by subcutaneous injection of lipopolysaccharide (100 ug). The mice were sacrificed on day 21 for EAU and at 24 h for EIU and eyes were immediately enucleated for histological and biochemical studies. Spleen-derived T-lymphocytes were used to study the antigen specific immune response in vitro.
EAU in WT mice caused severe damage to the retinal wall, especially to the photoreceptor layer, where as the damage was significantly less in ARKO mice or in WT mice treated with AR inhibitor, fidarestat. With EAU the levels of cytokines and chemokines were markedly increased in the eye tissues of WT mice but not in ARKO mice. Similarly, the cytokine levels were significantly elevated in WT EIU mice but not in ARKO mice with EIU. The T-lymphocytes isolated from WT mice but not from ARKO mice showed vigorous proliferation when exposed to the hIRPB antigen. The levels of inflammatory cytokines and chemokines were significantly elevated in T-lymphocytes isolated from WT mice but not from ARKO mice exposed to hIRBP.
Our results indicate that AR plays a pivotal role in the pathophysiology of uveitis complications and suggest that AR inhibition could be beneficial in the treatment of ocular inflammatory complications, especially uveitis.
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