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Timothy S Kern, Jie Tang, Haitao Liu, Krzysztof Palczewski, Yunpeng Du; Photoreceptors influence retinal vascular degeneration: retinal degeneration and diabetes. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2269. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Photoreceptor degeneration is associated with impaired function or structure of the retinal capillary network, but conversely, the presence of retinal photoreceptors has been implicated in the degeneration of the retinal microvasculature in diabetic retinopathy. To investigate how both the absence and presence of photoreceptors could affect the vasculature, we compared two mouse models of photoreceptor degeneration (opsin-/- and P23H mutant opsin knockin) with respect to their effect on retinal oxidative stress and on retinal capillary degeneration in nondiabetic and diabetic animals.
Retinal superoxide was measured at 2, 4 and 10 months of age by the luciginen assay. Capillary degeneration was assessed at 10 months of age (8 months diabetes) using the elastase digestion method.
Retinal photoreceptors did not degenerate in wildtype animals (nondiabetic or diabetic), and diabetes of 8 months duration in these mice significantly increased retinal capillary degeneration (as expected). In contrast, neither model of photoreceptor degeneration had any photoreceptors by 4 months of age, but there was extensive capillary degeneration in both models, even in the nondiabetic animals. In the mutant models, diabetes did not exacerbate the capillary degeneration compared to nondiabetics. While the photoreceptors were degenerating in the mutants, the retina showed a significant increase in stress (as evidenced by superoxide generation) that diminished in the opsin-/- (but not P23H mutants) after the photoreceptors had degenerated.
Retinal photoreceptors have a significant effect on the integrity and function of the retinal vasculature. Since we previously showed that oxidative stress plays an important role in the capillary degeneration in diabetic retinopathy, we postulate that the degeneration of retinal capillaries in retinal degeneration occurred while the photoreceptors were stressed and degenerating. In diabetes, photoreceptors do not degenerate, but they do develop the oxidative stress, and thus likely contribute to diabetes-induced retinal capillary degeneration.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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