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N.H. Timothy, A.C. Clermont, S. Rook, K.M. Della Vecchia, I. Mett, A. Faerman, O. Mor, E. Feinstein, L.P. Aiello; Diabetes–Induced Abnormalities in Retinal Vascular Permeability (RVP) & Electroretinogram (ERG) Are Normalized in RTP801/REDD1 Knockout (KO) Mice . Invest. Ophthalmol. Vis. Sci. 2005;46(13):427.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have previously identified and cloned hypoxia inducible gene RTP801/REDD1 that promotes neuronal cell apoptosis and generation of reactive oxygen species in vitro. Moreover, we found that in RTP801 knockout (KO) mice, physiologic neonatal retinal neovascularization (NV) is preserved under hyperoxic conditions and pathologic NV is reduced under hypoxic conditions. This study examines whether deletion of the RTP801 gene suppresses diabetes–induced abnormalities in the retina. Methods: Diabetes was induced in 8wk old RTP801 KO and C57/129sv wildtype (WT) littermate mice by intraperitoneal injection of STZ. After 4 weeks, ERG (single white flash, 1.4x104 cd/m2, 5 ms) was obtained from the left eye after 1 hour of dark adaptation. RVP was assessed from both eyes using the Evans–blue albumin permeation technique. Results: Blood glucose was not different between diabetic (DM) WT and DM KO (495±109 vs 513±76 mg/dl), nor nondiabetic (NDM) WT and KO (130±10 vs 135±31 mg/dl, respectively). RVP in the DM WT group was increased 138% (51.2 ± 37.9 µL/g/hr, n=8) compared to NDM WT (21.5 ± 18.8 µL/g/hr, n=9, p=0.055). In contrast, RVP was reduced by 81% in DM KO (9.5 ± 8.5 µL/g/hr, n=6, p=0.023) as compared to the DM WT mice, resulting in a 140% decrease of diabetes–induced RVP. In DM WT mice, there was a prolongation (p<0.05) of the oscillatory potential implicit times for OP2 (11%), OP3 (12%), & OP4 (14%) and for the B–wave (23%) as compared to NDM WT. A–wave was not significantly changed. These changes were normalized ∼100% in DM KO mice for OP3 & OP4 and 65% for B–wave as compared to NDM KO.Conclusions:Knock out of RTP801 ameliorates diabetes–induced RVP and ERG abnormalities in mice, suggesting that this hypoxia inducible gene may serve an important role in the pathogenesis of early diabetic retinal disease.
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