Functional Changes in the Adult Mouse Retina using an Alpha7 Nicotinic Acetylcholine Receptor Agonist after Blast Exposure

• Published in: Neuroscience Vol. 512; pp. 1 - 15
• Main Authors: Spitsbergen, Jake B., Webster, Sarah E., Linn, Cindy L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 21.02.2023
• Subjects: alpha7 nAChR agonist; alpha7 Nicotinic Acetylcholine Receptor; Animals; Bridged Bicyclo Compounds - pharmacology; ERG; Mice; Mice, Transgenic; Müller glia; Nicotinic Agonists - pharmacology; PNU-282987; Receptors, Nicotinic; Retina; PBS; KAX; Müller glia; DMSO; RPE; INL; PSI; DAPI; PNU-282987; PFA; ONL; MDPC; RGC; GCL; FFS; retina; ANOVA; nAChR; PhNR; MG; alpha7 nAChR agonist; ERG
• ISSN: 0306-4522; 1873-7544; 1873-7544
• DOI: 10.1016/j.neuroscience.2022.12.017

•Changes of retinal function after treatment with PNU-282987.•PNU-282987 affects ERG activity after blast trauma.•Retinal ganglion cells extend axons into optic nerve after PNU-282987 treatment.•PNU-282987 induces changes of retinal neurons after blast exposure.•PNU-282987 prevents amplitude decrease in ERG waveforms after blast. Currently, there is a lack of treatments for retinal neurotrauma. To address this issue, this study uses an alpha7 nAChR agonist, PNU-282987, to determine it effects on functional activity in the retina shortly after a traumatic blast exposure. The objectives of this research include: (1) examination of the cellular and functional damage associated with ocular blast exposure, and (2) evaluation of structural and functional changes that occur post PNU-282987 treatment. Significant ocular blast damage was induced in adult mice after exposure to a single blast of 35 psi to the left eye. Blast-exposed transgenic mice expressing tdTomato Müller glia were treated daily with eyedrops containing PNU-282987 for 4 weeks following the blast exposure. Antibody staining studies in these transgenic mice was conducted to examine lineage tracing and electroretinograms (ERGs) were obtained to examine functional changes. Blast exposure caused a significant loss of cells in all retinal layers after 4 weeks. Immunohistochemical analysis demonstrated tdTomato-positive labeled photoreceptors and retinal ganglion cells in blast-exposed mice treated with PNU-282987. ERG recordings were taken from control animals, from blast-damaged animals and from animals exposed to blast followed by 4 weeks of PNU-282987 treatment. Scotopic ERG recordings from blast-exposed mice had significantly decreased amplitudes of a-wave, b-wave, oscillatory potentials and flicker frequencies, which were prevented after PNU-282987 treatment. In photopic experiments, the PhNR response was reduced significantly after blast exposure but the decrease was prevented after treatment with PNU-282987. These are the first experiments that demonstrate preservation of retinal function after blast exposure using an alpha7 nAChR agonist.