Retinal ganglion cell degeneration in glaucoma disrupts HPA axis temporal organization and dampens corticosterone production

Apr 24, 2026Journal of neuroendocrinology

Damage to eye nerve cells in glaucoma disrupts daily stress hormone patterns and lowers hormone levels

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Abstract

Glaucoma may disrupt the coordination of the hypothalamic-pituitary-adrenal (HPA) axis, as indicated by altered gene expression profiles.

Reduced expression of the Crh gene was observed in the paraventricular nucleus of glaucoma-affected mice.
A 10-hour phase delay in the expression of the Crh-r1 gene was noted in the pituitary gland due to glaucoma.
The rhythmic expression of Pomc in the pituitary and Mc2r in the adrenal gland was lost in glaucoma-affected mice.
Changes in the daily rhythms of key clock genes were associated with alterations in the HPA axis gene expression profiles.
The observed phase shifts and amplitude changes in Per1, Per2, Nr1d1, and Bmal1 resulted in misalignment of pituitary and adrenal rhythms.
Reduced amplitude of corticosterone was linked to impaired communication between central and peripheral biological clocks.

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Glaucoma is a chronic optic neuropathy characterized by progressive vision loss. A previous study from our group showed that glaucoma-induced retinal degeneration disrupts photic signaling to the suprachiasmatic nucleus (SCN), altering the molecular components of the central circadian clock. Through its hypothalamic projections, the SCN entrains the hypothalamic-pituitary-adrenal (HPA) axis and drives the rhythmic secretion of corticosterone. In this study, we investigated whether central circadian clock disruption in glaucoma impacts the HPA axis and its downstream physiological rhythms. We analyzed the temporal profiles of key genes controlling the HPA axis in mice with glaucoma. The Crh gene expression was reduced in the paraventricular nucleus, while Crh-r1 exhibited a 10-h phase delay in the pituitary in response to glaucoma. Additionally, Pomc in the pituitary and Mc2r in the adrenal lost rhythmicity. The modulation of the daily rhythms of these key genes was associated with alterations in the diurnal rhythms of clock genes in the PVN, pituitary and adrenal gland. Glaucoma-induced phase shifts and amplitude alterations in the rhythmic expression of Per1, Per2, Nr1d1, and Bmal1 in the pituitary and adrenal gland, resulted in a temporal misalignment between the pituitary and adrenal rhythms. These molecular changes were associated with reduced corticosterone amplitude, suggesting impaired communication between central and peripheral clocks. Together, these findings demonstrate that glaucoma alters the temporal coordination of the HPA axis, highlighting how retinal dysfunction can propagate beyond the visual system to disturb systemic circadian and neuroendocrine regulation.

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Retinal ganglion cell degeneration in glaucoma disrupts HPA axis temporal organization and dampens corticosterone production

Abstract

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