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D. Gu, G. Acland, S. Pearce–Kelling, A. Cideciyan, T. Alemán,, S. Jacobson, G. Aguirre; Light–Dependent AP–1 Activation in the T4R Rhodopsin (RHO) Mutant Dog . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1707.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Retinal illumination, at levels typically used in clinical examinations, dramatically accelerates photoreceptor degeneration in the T4R RHO mutant dog. We examined whether AP–1 activation is associated with light–induced disease acceleration in the T4R RHO retina. Methods: T4R+/– and control dogs were dark adapted overnight; both eyes of each dog were dilated with mydriatics; each right eye was patched with an opaque dressing; the fundus of each left eye was then examined by indirect ophthalmoscopy, and photographed (∼25 overlapping frames) using a Kowa RC–2 fundus camera. Dogs remained in the dark until sacrificed at 1 or 6 hours after exposure. AP–1 activation was determined by electrophoretic mobility shift assays (EMSA) of retinal nuclear protein extracts hybridized with labeled AP–1 consensus oligonucleotide, and analyzed on 2–20% gradient polyacrylamide gels. The DNA binding activity of AP–1 was assessed by evaluating the intensity of the shifted bands representing the AP–1/oligonucleotide complex. Results: Increased AP–1 levels (∼ 4 fold) were observed in the light exposed mutant retinas by 1 hr after exposure, and remained elevated at 6 hr. The non–exposed eyes had AP–1 levels comparable to the normal or dark–adapted mutant retina not exposed to light. The same light exposure protocol was done in dogs affected with a non–allelic retinal degeneration (prcd) with similar phenotype, and showed no AP–1 activation after light exposure. Conclusions: Light exposures that are non–damaging to the normal retina result in early AP–1 activation in the T4R RHO mutant dog retina. Such activation may link the environmental insult to photoreceptor degeneration.
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