Purchase this article with an account.
Peter Baciu, Eric Sung, Jason Guu, Howard Rind, George ehring; Accelerated Retinal Degeneration and Progressive RPE Dystrophy by Oxidative Stress in a Retinal Angiomatous Proliferation (RAP) Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4779.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Oxidative stress has been identified as a key mechanism in leading to retinal degeneration in the vldlr null mouse1. The purpose of this study is to determine if the level of retinal degeneration in vldlr deficient mouse is enhanced by removal of sod1 gene.
vldlr null mice were back crossed onto the sod1 leb/j C57b/6 null background and the levels of RPE dystrophy, retinal function, and neovascular response followed at 4 and 6 months of age. RPE dystrophy was monitored by both color fundus and I/R imaging using HRA2 SLO fitted with a 55o lens. Neovascularization was monitored by flourescien angiography. Retinal Structural and functional changes were monitored by H&E staining, OCT and scotopic ERG.
Consistent with observations reported in the literature1 vldlr null mice showed modest deficits in scotopic ERG at 4 and 6 months of age. Sod1 -/- mice had no loss in scotopic A and B wave amplitudes. However, vldlr/sod1 double knockout mice had a significantly decreased scotopic A and B wave amplitudes and oscillatory potential relative to wild type, sod1 -/- or vldlr -/- animals by 2 months. Examination of sod -/- and sod -/+ on a vldlr null background indicated that the level of functional deficit was dependent on sod1 copy number. The functional deficits observed by ERG correlated with a significant reduction in ONL thickness as measured by OCT and H&E staining. Color fundus identified localized RPE dystrophy in the vldlr -/- mice while in the sod1/vldlr double knockout a wide-spread RPE dystrophy was observed. Angiography indicated similar patterns of subretinal neovascularization in both the vldlr -/- and the vldlr/sod1 double knockout mice.
Reduction in anti-oxidant defense through removal of the sod1 gene significantly accelerated the functional deficits see in the vldlr -/- animals. The level of deficit was coupled to the presence of the sod1 gene with sod-/- showing greater loss than sod-/+ animals suggesting a direct effect of oxidative stress mechanism on photoreceptor function. Unique to our observations was the pronounced expansion of RPE dystrophy in the DKO mouse.1 J. Clin. Invest 119:611-623(2009)
This PDF is available to Subscribers Only