Gpr75 knockout mice display age-dependent cone photoreceptor cell loss.

GPR75 is an orphan G protein-coupled receptor for which there is currently limited information and its function in physiology and disease is only recently beginning to emerge. This orphan receptor is expressed in the retina but its function in the eye is unknown. The earliest studies on GPR75 were conducted in the retina, where the receptor was first identified and cloned and mutations in the receptor were identified as a possible contributor to retinal degenerative disease. Despite these sporadic reports, the function of GPR75 in the retina and in retinal disease has yet to be explored. To assess whether GPR75 has a functional role in the retina, the retina of Gpr75 knockout mice was characterized. Knockout mice displayed a mild progressive retinal degeneration, which was accompanied by oxidative stress. The degeneration was because of the loss of both M-cone and S-cone photoreceptor cells. Housing mice under constant dark conditions reduced oxidative stress but did not prevent cone photoreceptor cell loss, indicating that oxidative stress is not a primary cause of the observed retinal degeneration. Studies here demonstrate an important role for GPR75 in maintaining the health of cone photoreceptor cells and that Gpr75 knockout mice can be used as a model to study cone photoreceptor cell loss.