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Emily Levine, Robert Zawadzki, Hwai-Jong Cheng, Scott Simon, Edward Pugh, Marie Burns; Early indications of pending degeneration in a mouse model of photoreceptor light damage. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4179.
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Photoreceptor degeneration is a common outcome of both congenital mutations in phototransduction proteins and environmental stress, including light-induced damage. In mice lacking the protein visual arrestin (Arr1), normal cyclic light causes an accelerated, age-related apoptosis of photoreceptors and thinning of the outer nuclear layer of the retina. We have investigated the progression of this light-dependent degeneration in vivo, as well as the involvement of microglia, neutrophils and macrophages in the clearing of the outer nuclear layer following light exposure.
Young adult mice were bred and housed in 24 hr darkness before being exposed to normal 12:12 cyclic light at 4-6 weeks of age. The retinas were examined using AO-OCT and standard immunocytochemical methods at time points ranging from hours to weeks.
The retinas of arr1-/- mice born and reared in darkness were not significantly different from wild-type mice reared in normal cyclic light. After transferring arr1-/- mice into cyclic light, the outer nuclear layer thickness was slightly reduced in localized regions of the retina within 1 week. However, there was a marked increase in the number of microglia in the retina, and a larger fraction of them were localized to the photoreceptor layer than in dark-adapted arr1-/- retinas. Although very few neutrophils were present in age-matched wild-type or dark-reared arr1-/- retinas, the number of neutrophils present in the light-exposed arr1-/- progressively increased over the first days and weeks of cyclic light exposure.
Light-induced photoreceptor stress in this animal model at early times causes the proliferation of microglia and the recruitment or increased retention time of neutrophils in the retina. These changes precede gross morphological changes in the photoreceptors and as such appear to be early indicators for photoreceptor stress and pending degeneration.
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