Glaucoma Inducing Retinal Ganglion Cell Degeneration Alters Diurnal Rhythm of Key Molecular Components of the Central Clock and Locomotor Activity in Mice

Glaucoma is a chronic optic neuropathy characterized by the progressive de- generation of retinal ganglion cells (RGC). These cells play a crucial role in transmitting visual and non-visual information to brain regions, including the su- prachiasmatic nucleus (SCN), responsible for synchronizing biological rhythms. To understand how glaucoma affects circadian rhythm synchronization, we in- vestigated potential changes in the molecular clock machinery in the SCN. We found that the progressive increase in intraocular pressure (IOP) negatively correlated with spontaneous locomotor activity (SLA). Transcriptome analy- sis revealed significant alterations in the SCN of glaucomatous mice, including downregulation of genes associated with circadian rhythms. In fact, we showed a loss of diurnal oscillation in the expression of vasoactive intestinal peptide (Vip), its receptor (Vipr2), and period 1 (Per1) in the SCN of glaucomatous mice. These findings were supported by the 7-h phase shift in the peak expression of arginine vasopressin (Avp) in the SCN of mice with glaucoma. Despite maintaining a 24-h period under both light/dark (LD) and constant dark (DD) conditions, glaucoma- tous mice exhibited altered SLA rhythms, characterized by decreased amplitude. Taken altogether, our findings provide evidence of how glaucoma affects the regulation of the central circadian clock and its consequence on the regulation of circadian rhythms.