Neuronal Bmal1 regulates retinal angiogenesis and neovascularization in mice

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Summary

Disruption of the circadian clock gene Bmal1 in retinal neurons leads to angiogenic defects and reduced pathological neovascularization, mimicking effects seen under constant light exposure, with semaphorin signaling identified as a dominant downstream pathway. These findings suggest that light environment management in neonatal and clinical settings may have direct implications for retinal vascular disease progression, and that therapeutic targeting of the retinal clock could treat conditions like diabetic retinopathy and retinopathy of prematurity.

Key Findings

Deletion of Bmal1 and Per2 from retinal neurons resulted in retinal angiogenic defects similar to those observed in animals maintained under constant light conditions.
Neuronal Bmal1 deletion reduced pathological neovascularization with reduced vascular leakage in two different neovascularization models.
Chromatin immunoprecipitation sequencing identified semaphorin signaling as the dominant pathway regulated by Bmal1 in retinal neurons.
Embryonic retina requires light cues to maintain robust circadian expression of the core clock gene Bmal1, establishing a causal link between light environment and retinal clock function.

Categories

Eye Health & Vision: Directly investigates retinal angiogenesis, neovascularization, and retinopathies in relation to circadian clock gene function.

The Science of Light: Demonstrates that light-dark cycles are required for robust circadian Bmal1 expression in the embryonic retina, linking phototransduction to clock gene regulation.

Neonatal Care: Findings are relevant to retinopathy of prematurity, suggesting circadian clock modulation as a therapeutic target in neonatal retinal disease.