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Updated: Jan 11, 2026

Retinal Explant of the Adult Mouse Retina as an Ex Vivo Model for Studying Retinal Neurovascular Diseases
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Endothelial clock regulates retinal angiogenesis and ganglion cell function.

Vijay K Jidigam1, Madison B Kirby1, Joshua Gallop1

  • 1Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.

Angiogenesis
|November 15, 2025
PubMed
Summary

Circadian clock genes Bmal1 and Per2 are crucial for retinal angiogenesis and vascular endothelial cell proliferation. Their disruption impairs vessel growth and retinal function, highlighting the importance of biological clocks in vascular development.

Keywords:
AngiogenesisCell cycleERGEndothelial clockPhNRRGCs

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Area of Science:

  • Vascular biology
  • Chronobiology
  • Ophthalmology

Background:

  • Angiogenesis is vital for development and disease, regulated by intrinsic and extrinsic factors.
  • Biological clocks (circadian rhythms) influence physiological processes, including angiogenesis via factors like Vegfa.
  • The interplay between circadian rhythms and angiogenic processes is an emerging area of research.

Purpose of the Study:

  • To investigate the role of circadian clock genes Bmal1 and Per2 in retinal angiogenesis.
  • To understand how these genes affect vascular endothelial cell (VEC) proliferation and retinal circuitry.

Main Methods:

  • Endothelial cell-specific deletion of Bmal1 and Per2 in mouse models.
  • RNA-sequencing (RNA-seq) analysis of retinal endothelial cells.
  • Assessment of retinal vessel growth, VEC proliferation, and retinal ganglion cell (RGC) numbers.

Main Results:

  • Deletion of Bmal1 and Per2 significantly impaired retinal angiogenesis.
  • Circadian clocks primarily regulate genes involved in cell proliferation.
  • Bmal1 knockout disrupted diurnal VEC proliferation, increased Brn3a-positive RGCs, and compromised retinal function.

Conclusions:

  • Bmal1 and Per2 play critical roles in regulating retinal angiogenesis.
  • Circadian control of cell proliferation is essential for proper vascular development and retinal function.
  • Disruption of circadian clock genes impacts retinal circuitry and overall function.