ORIGINAL RESEARCH article
Front. Neurosci.
Sec. Visual Neuroscience
This article is part of the Research TopicRetinal Neuroprotection: Exploring Novel and Repurposed TherapeuticsView all articles
An Alpha7 Nicotinic Acetylcholine Receptor Agonist Induces Retinal Neurogenesis and Restores Electrophysiological Function Following Blast-Induced Ocular Trauma in Adult Mice
Provisionally accepted- 1Western Michigan University Libraries, Kalamazoo, United States
- 2Western Michigan University, Kalamazoo, United States
- 3Grand Valley State University, Allendale, United States
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Blast-induced ocular trauma is one of the leading causes of vision loss in civilian and military populations. However, current treatments are limited by the adult mammalian retina's inability to regenerate neurons lost to damage, disease, and aging. This study investigates the neurogenic potential of PNU-282987, a nicotinic acetylcholine receptor agonist, in an adult mouse model of blast-induced ocular trauma. Experiments were designed to determine if a delayed treatment paradigm, initiated after significant neuronal loss in the retina had already occurred, could induce neurogenesis and restore visual function. One month after delivery of a single blast, adult mice demonstrated a significant decrease in cell counts across all retinal layers and there was a corresponding reduction in recorded electroretinogram amplitudes. After the blast was delivered and loss of neurons was established, daily eye drops containing PNU-282987 were administered for two weeks. Following this delayed treatment, morphological analysis revealed robust cellular proliferation and neurogenesis, confirmed by BrdU incorporation with co-labelling of retinal ganglion cells and photoreceptors. Cell counts in PNU-282987 treated retinas increased significantly compared to untreated blasted eyes, returning to a level that was not significantly different from control retinas. Electrophysiological recordings also demonstrated a significant recovery of retinal function to baseline levels or beyond. This work establishes a promising novel approach for treating retinal damage, as PNU-282987-induced neurogenesis is sufficient to restore retinal ERG function in a blast damaged mammalian adult retina.
Keywords: Neurogenesis, Retina, Electrophysiology, photoreceptor, retinal ganglion cell, blast injury, BrdU
Received: 22 Sep 2025; Accepted: 12 Nov 2025.
Copyright: © 2025 Nolasco de Carvalho, Spitsbergen, Linn and Linn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Cindy L Linn, cindy.linn@wmich.edu
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