Novel role for v5-integrin in retinal adhesion and its diurnal peak

v5-Integrin is the sole integrin receptor at the retinal pigment epithelium (RPE)-photoreceptor interface and promotes RPE phago-cytic signaling to the tyrosine kinase Mer tyrosine kinase (MerTK) once a day in response to circadian photoreceptor shedding. Herein we identify a novel role for v5-integrin in permanent RPE-photorecep-tor adhesion that is independent of v5’s function in retinal phago-cytosis. To compare retinal adhesion of wild-type and 5-integrin/ mice, we mechanically separated RPE and neural retina and quantified RPE protein and pigment retention with the neural retina. Lack of v5-integrin with normal expression of other RPE integrins greatly weakened retinal adhesion in young mice and accelerated its age-dependent decline. Unexpectedly, the strength of wild-type retinal adhesion varied with a diurnal rhythm that peaked 3.5 h after light onset, after the completion of phagocytosis, when integrin signaling to MerTK is minimal. Permanent v5 receptor deficiency attenuated th