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Neuronal Bmal1 regulates retinal angiogenesis and neovascularization in mice
Vijay K Jidigam1, Onkar B Sawant1,2, Rebecca D Fuller1
1Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Communications Biology
|August 6, 2022
Summary
The mammalian retinal circadian clock regulates vision and adaptation to light. Disrupting clock genes like Bmal1 causes retinal angiogenic defects, suggesting clock silencing as a potential treatment for retinopathies.
Area of Science:
- Ophthalmology
- Chronobiology
- Molecular Biology
Background:
- Mammalian retinal circadian clocks regulate daily functions and adaptation to light-dark cycles.
- A link between circadian clocks and retinopathies is suggested but not causally established.
Purpose of the Study:
- To investigate the role of circadian clock genes in retinal development and neovascularization.
- To determine if targeting the retinal clock could treat retinopathies.
Main Methods:
- Studied clock gene expression in embryonic mouse retinas.
- Utilized genetic deletion of Bmal1 and Per2 in retinal neurons.
- Assessed pathological neovascularization in two disease models.
- Performed chromatin immunoprecipitation sequencing.
Main Results:
- Embryonic retinas require light cues for robust Bmal1 expression.
- Bmal1 and Per2 deletion caused retinal angiogenic defects.
- Neuronal Bmal1 deletion reduced pathological neovascularization and vascular leakage.
- Semaphorin signaling was identified as a key Bmal1-regulated pathway.
Conclusions:
- A dysregulated retinal circadian clock drives pathological neovascularization.
- Therapeutic silencing of the retinal clock may treat retinopathies such as diabetic retinopathy and retinopathy of prematurity.
