A hypothetical circadian‒endocrine pathway linking melanopsin-expressing ipRGC dysfunction in autoimmune retinopathy...

Autoimmune Retinopathy (AIR) is a rare, immune-mediated retinal degeneration caused by circulating autoantibodies targeting retinal antigens. Although classically associated with photoreceptor loss, multiple clinical and experimental studies suggest broader inner retinal involvement, including retinal ganglion cells.

This review proposes a novel, hypothesis-generating model based on existing literature, exploring whether AIR may contribute to circadian disruption and sexual dysfunction-particularly erectile dysfunction (ED)-through immune-mediated injury to melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs).

ipRGCs project to the suprachiasmatic nucleus (SCN) and are essential for synchronizing circadian rhythms and regulating neuroendocrine function. While direct evidence of ipRGC damage in AIR is lacking, ipRGC pathway dysfunction has been reported in glaucoma and diabetic retinopathy-conditions that share pathological mechanisms with AIR. Circadian misalignment may disrupt testosterone secretion, melatonin rhythms, and nitric oxide signaling, all of which are implicated in ED.

This interdisciplinary framework integrates ocular immunology, circadian biology, and sexual medicine to highlight a potentially overlooked systemic dimension of AIR. Future studies are warranted to evaluate ipRGC integrity and circadian-endocrine markers in AIR patients and validate this conceptual pathway.