Slowed Photoresponse Recovery and Age-Related Degeneration in Cones Lacking Gprotein-Coupled Receptor Kinase 1

Neovascularization, Enhanced Inflammatory Response, and Age-Related Cone Dystrophy in theNrl−/−Grk1−/−Mouse Retina

“…Unlike the rod photoreceptors of the Grk1 Ϫ/Ϫ mouse, which degenerate rapidly when exposed to light because of the inability to inactivate phototransduction, 14 cones lacking Grk1 expression on the Nrl Ϫ/Ϫ background degenerate by apoptosis in the dark. 15 The present study extends our initial observations and demonstrates that in addition to a delayed photoresponse recovery, the absence of Grk1 expression leads to age-related and light-independent cone dystrophy with abnormal vascularization in the retinas of Nrl Ϫ/Ϫ Grk1 Ϫ/Ϫ mice compared with Nrl Ϫ/Ϫ . To facilitate the identification of potential genes involved in biological and disease pathways, we identified key molecular networks to characterize the Nrl Ϫ/Ϫ Grk1 Ϫ/Ϫ phenotype.…”

“…Retinal cross-sections from Nrl Ϫ/Ϫ and Nrl Ϫ/Ϫ Grk1 Ϫ/Ϫ retinas were immunohistologically stained with pAB S-and Mopsin antibodies and confirmed our previous observations 15 that both S and M cones degenerate in the Nrl Ϫ/Ϫ Grk1 Ϫ/Ϫ mouse retina in an age-dependent manner (Supplementary Fig. S1; Supplementary Figures and Tables available at http://www.…”

“…2E, 2F). 15 Cone-specific Arr4 immunoreactivity and H&E staining confirm that the thinning of the retina in 5-and 9-month-old…”

“…14 Moreover, Grk1 null mice have a delayed recovery of photopic response in both the rod-dominant 5 and the "all-cone" Nrl Ϫ/Ϫ mouse retina. 3,15 In this study, we observed for the first time that the cone photoreceptors of Nrl Ϫ/Ϫ mice lacking Grk1 expression degenerate with increasing age in a manner that is independent of their environmental light exposure (Fig. 1).…”

“…[15][16][17] The Nrl Ϫ/Ϫ and Nrl Ϫ/Ϫ Grk1 Ϫ/Ϫ mice maintained in total darkness, ambient (ϳ5 lux) cyclic light, or bright (ϳ8000 lux) constant light were recorded at 1, 3, 5, 7, and 9 months of age. At least 10 mice were recorded for each genotype at each age.…”