Biological rhythms in retinal development Demystifying the eye

This thesis investigated the role of the circadian clock during the development of the mouse retina until adulthood. The Period1 (Per1) and Period2 (Per2) genes underlying the retinal clock have been involved in cell division as well as in the retinal ontogeny modus operandi. The Per1/Per2 double mutant mice show a delay in general photoreceptor differentiation, along with reductions in cone opsin mRNA and protein levels. In light of. these observations, we further provided the evidence that during development Per1/Per2 ablation significantly affects gene expression of the phototransduction pathway and cell cycle components, as well as the secondary regulatory loop members of the circadian clockwork. We showed that mice deficient for core circadian clock genes (Per1 and Per2) lack a daily peak in photoreceptor outer segment (POS) phagocytosis under constant darkness. We have also found an impaired daily modulation of visual sensitivity during the inactivation of Per1 and Per2 genes as compared to the wild-type mice. Besides, we have also explored clinical perspectives by examining Bmal1 gene mutations in probands of consanguineous congenital cataract families and generated a systematic analysis of the current patient-reported outcome measures (PROM) used in human clinical trials.