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D. Raz, S. Machida, R.N. Fariss, C. Vijayasarathy, R.A. Bush, P.A. Sieving; Origins of the Photopic Negative Response in Rat Retinal Degeneration Models . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2248.
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Purpose: The primate light adapted electroretinogram (ERG) has a negative deflection (PhNR) following the b–wave that is associated with ganglion cells and axons. We explored the retinal origins of the PhNR in the rat during retinal degeneration. A propos the known potassium mechanism and amacrine cell origin of the scotopic threshold response we are exploring whether the photopic component has similar origins. Methods: Royal College of Surgeons (RCS) rats and p23h rhodopsin transgenic rats at different stages of retinal degeneration were used. Photopic ERG’s were recorded with a 0.6 log cd–s/m2 xenon flash on a background light of 34 cd/m2. Eyes were removed after euthanasia. Retinas were immunolabeled for Kir4.1, the dominant potassium channel on Mueller glial cells responsible for currents generating the ERG in the inner retina. An antibody developed against the peptide corresponding to residues 356–375 of rat Kir4 was used for immunolabeling. Whole cell lysates were prepared from retinas and run on a native polyacrylamide gel. The tetrameric form of Kir4.1 was detected by immunoblot analysis using the same antibody. Additional studies are being performed involving optic nerve transection, TTX and potassium channel blockers. Results: The PhNR increased in RCS rats as retinal degeneration progressed, but gradually declined in p23h rats, whereas the b–wave decreased in both forms of degeneration. Immunolabeling revealed an apparent Kir4.1 increase in the inner plexiform and ganglion cell layers in the RCS rats with age, in agreement with the immunoblots. Kir4.1 immunolabeling in p23h rats did not change in the proximal retina with degeneration, but increased in the RPE. Conclusions: The PhNR may originate in potassium currents in the inner retina. Although both RCS and p23h retinal degenerations are characterized by photoreceptor death, the photopic ERG’s and the PhNR indicate that they involve a different set of events.
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