Novel role for αvβ5-integrin in retinal adhesion and its diurnal peak
αvβ5-Integrin is the sole integrin receptor at the retinal pigment epithelium (RPE)-photoreceptor interface and promotes RPE phagocytic 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 αvβ5-integrin in permanent RPE-photoreceptor adhesion that is independent of αvβ5's function in retinal phagocytosis. To compare retinal adhesion of wild-type and β 5 -integrin −/− mice, we mechanically separated RPE and neural retina and quantified RPE protein and pigment retention with the neural retina. Lack of αvβ5-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 αvβ5 receptor deficiency attenuated the diurnal peak of retinal adhesion in β 5 -integrin −/− mice. These results identify αvβ5-integrin as the first RPE receptor that contributes to retinal adhesion, a vital mechanism for long-term photoreceptor function and viability. Furthermore, they indicate that αvβ5 receptors at the same apical plasma membrane domain of RPE cells fulfill two separate functions that are synchronized by different diurnal rhythms.