Glial cells expressing visual cycle genes are vital for photoreceptor survival in the zebrafish pineal gland

Abstract

Photoreceptors in the vertebrate eye are dependent on the retinal pigmented epithelium for a variety of functions including retinal re‐isomerization and waste disposal. The light‐sensitive pineal gland of fish, birds, and amphibians is evolutionarily related to the eye but lacks a pigmented epithelium. Thus, it is unclear how these functions are performed. Here, we ask whether a subpopulation of zebrafish pineal cells, which express glial markers and visual cycle genes, is involved in maintaining photoreceptors. Selective ablation of these cells leads to a loss of pineal photoreceptors. Moreover, these cells internalize exorhodopsin that is secreted by pineal rod‐like photoreceptors, and in turn release CD63‐positive extracellular vesicles (EVs) that are taken up by pdgfrb‐positive phagocytic cells in the forebrain meninges. These results identify a subpopulation of glial cells that is critical for pineal photoreceptor survival and indicate the existence of cells in the forebrain meninges that receive EVs released by these pineal cells and potentially function in waste disposal.

Cross‐species single‐cell landscape of vertebrate pineal gland

“…Interestingly, RPE-like cells also play a role in the retinoid cycle of the pineal gland 34 and Agrp2-expressing RPE-like cells are essential for photoreceptor viability and melanocyte-associated background adaptation in zebrafish. 82,83 These findings collectively suggest that glial cells in the pineal gland may play a role in the regulation of circadian rhythms, a hypothesis that warrants further investigation and validation. In contrast, the pineal glands of mammals were predominantly composed of pinealocytes, accounting for approximately 85% in rats and 95% in monkeys, with a smaller proportion made up of astrocytes, constituting around 7% in rats and 2% in monkeys.…”

“…Furthermore, RPE‐like and Müller‐like glia cells exhibited the expression of phototransduction‐related genes, including exorh , saga , pde6h , gngt1 , and gnat1 , indicating their potential involvement in photoreception. Interestingly, RPE‐like cells also play a role in the retinoid cycle of the pineal gland 34 and Agrp2 ‐expressing RPE‐like cells are essential for photoreceptor viability and melanocyte‐associated background adaptation in zebrafish 82,83 . These findings collectively suggest that glial cells in the pineal gland may play a role in the regulation of circadian rhythms, a hypothesis that warrants further investigation and validation.…”