Hyperglycemia Activates Retinal Photoreceptors to Induce Neuroglial Inflammation

Huerta, I. D. l.; Uddin, M. I.; Penn, J. S.

doi:10.64898/2026.08.27.747567

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bioRxiv · 10.64898/2026.08.27.747567

Hyperglycemia Activates Retinal Photoreceptors to Induce Neuroglial Inflammation

Huerta, I. D. l.·Uddin, M. I.·Penn, J. S.

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Abstract

Abstract Diabetic retinopathy (DR) is a major cause of vision loss in working-age adults. Accumulating evidence suggests that retinal photoreceptors contribute to the initiation and progression of diabetic retinopathy. In this study, we investigated whether hyperglycemia directly alters photoreceptor signaling and whether photoreceptor-derived inflammatory mediators activate downstream Muller glial cells. Primary photoreceptors were isolated from adult mice and cultured with normal glucose, high D-glucose, or high L-glucose as an osmotic control. Photoreceptorconditioned media were analyzed for inflammatory and growth factors and used to stimulate primary Muller glia. High glucose exposure increased photoreceptor production of TNF-a, IL-6, and VEGF. Photoreceptorconditioned media from high glucose-treated photoreceptors induced Muller glial expression of IL-1b, TNF-a, and IL-6. Muller glia exposed to photoreceptor-conditioned media increased VEGF expression and secretion and enhanced MMP-9 expression, secretion, and gelatinase activity. Together, these findings support a direct role for photoreceptors as glucose-responsive neuronal cells that can initiate and amplify neuroglial inflammatory signaling in hyperglycemic conditions.

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Huerta, I. D. l., Uddin, M. I., Penn, J. S.. 2026-09-01. Hyperglycemia Activates Retinal Photoreceptors to Induce Neuroglial Inflammation. https://doi.org/10.64898/2026.08.27.747567

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