Microglial Bmal1 Contributes to Diurnal Physiology and Retinal Homeostasis.

Area of Science:

• Neuroimmunology
• Chronobiology
• Ophthalmology

Background:

• Circadian rhythms influence immune responses, with microglia acting as key immune cells in the central nervous system.
• Microglial functions like surveillance and cytokine production show daily rhythms, regulated by clock genes.
• The role of circadian rhythms in retinal microglia, crucial for visual processing, remains unexplored.

Purpose of the Study:

• To investigate the presence and regulation of circadian rhythms in retinal microglia.
• To determine the impact of circadian disruption on retinal microglia and overall retinal health.

Main Methods:

• Analysis of clock gene expression in retinal microglia.
• Assessment of microglial morphology and inflammatory markers.
• Evaluation of retinal health and behavioral function in mice with Bmal1-deficient microglia.

Main Results:

• Retinal microglia exhibit circadian rhythms in clock gene expression, morphology, and inflammatory markers, dependent on the Bmal1 gene.
• Loss of Bmal1 in microglia leads to reduced retinal health and impaired behavioral function.
• Bmal1 deficiency induces a senescent, disease-associated microglia phenotype and transcriptomic changes in the retina.

Conclusions:

• Diurnal clock rhythms are essential for regulating retinal microglia physiology within the retinal niche.
• Circadian regulation by Bmal1 contributes to the homeostatic maintenance of the retinal tissue environment.
• Understanding microglial chronobiology may offer new therapeutic targets for retinal diseases associated with circadian disruption.