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S. C. Khani, K. Sakurai, J. E. Young, Z. K. Oskouie, L. Shefflin, C. Dlugos, V. J. Kefalov, T. Whitcomb; Rhodopsin Kinase Expression Levels and Photoreceptor Viability. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4469.
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© ARVO (1962-2015); The Authors (2016-present)
Visual pigment phosphorylation is the first of the two key steps in photoreceptor recovery and deactivation catalyzed by rhodopsin kinase or G protein dependent receptor kinase 1 (GRK1). Absence of GRK1 or its downstream partner arrestin leads to deficits in photoreceptor recovery along with heightened susceptibility to light-induced photoreceptor cell death. The purpose of the following study is to determine whether GRK overexpression might improve the viability of photoreceptors exposed to light stress.
Transgenic mouse retinas expressing excess GRK1 (GRK+) and wild type littermates (WT) were compared using isolated retinal ERG recordings, TUNEL staining, limited profiling of apoptotic molecules, nucleosome release assays and light microscopy. Comparisons were extended to conditions of intense light with mice reared on a moderately light-sensitive RPE65 Leu450Met heterozygous background.
GRK+ mice showed no physiologic or morphologic retinal deficit reared in room light. The transcript levels fror apoptosis-related molecule were also identical in GRK+ and WT retinas. Exposure to intense light led to comparable increase in soluble nucleosomes from GRK+ and WT retinas. Apoptotic activity was confined to the outer nuclei. Outer nuclear layer thickness was also reduced in both GRK+ and WT animals but the reduction was significantly greater in GRK+ animals.
GRK overexpression did not protect photoreceptor against light-induced damage and may have paradoxically increased their susceptibility to intense light. These findings along with other published work suggest a possible GRK-related cell death pathway in photoreceptors. This pathway may be in part apoptosis-independent.
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