Neurogenesis and Functional Recovery in the Adult Mouse Retina Using an Alpha7 nAChR Agonist after Blast Exposure
Date of Award
Master of Science
Cindy Linn, Ph.D.
Jeremy Duncan, Ph.D.
Christine Byrd-Jacobs, Ph.D.
Blast injury, electroretinogram, mice, neurogenesis, ocular trauma, retina
Masters Thesis-Abstract Only
Restricted to Campus until
Previous studies have provided evidence that eyedrop application of the selective α7 nicotinic acetylcholine receptor agonist, PNU-282987, induces neurogenesis and regeneration of retinal neurons from Müller glia in adult rodents. 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 recovery 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 were performed to study regeneration of new neurons derived from Müller glia and electroretinograms (ERGs) were obtained to examine functional recovery. Blast exposure caused a significant loss of cells in all retinal layers after 4 weeks. Immunohistochemical analysis demonstrated double-labeled tdTomato-positive 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 (OP) and flicker frequencies, which recovered after PNU-282987 treatment. In photopic experiments, the photopic negative response was reduced significantly after blast exposure but recovered after treatment with PNU-282987. These are the first experiments that demonstrate recovery of functional changes in the retina after blast exposure using an alpha7 nAChR agonist.
Spitsbergen, Jake Bennett, "Neurogenesis and Functional Recovery in the Adult Mouse Retina Using an Alpha7 nAChR Agonist after Blast Exposure" (2022). Masters Theses. 5360.