Date of Defense
4-19-2024
Date of Graduation
4-2024
Department
Biological Sciences
First Advisor
Cindy Linn
Second Advisor
John Spitsbergen
Abstract
Previous studies from this lab have explored the neurogenic capability of an alpha7 nicotinic acetylcholine receptor agonist, PNU-282987, in the retina. The goal of this study is to investigate the neurogenic effects of PNU-282987 in adult mouse retinas following blast-induced ocular trauma. Functional recovery and neurogenesis was evaluated using electroretinogram (ERG) recordings in dark adapted animals and immunohistochemistry. Blast injuries were induced in 3-8 month old adult mice with a 35-psi blast delivered to the left eye using a modified paintball gun. One month post blast, mice were treated bilaterally daily for two weeks with PBS eye drops containing either 1% DMSO/1 mg/mL BrdU or 1 mM PNU-282987/BrdU. ERG recordings were conducted before blast exposure and every week following blast exposure for two months. At the end of two months, retinas were processed immunohistochemically for BrdU incorporation and for retinal cell markers. ERG analysis revealed that the a-wave, b-wave, and oscillatory potential (OP1, 2, and 3) amplitudes all significantly decreased following blast injury. Once PNU-282987 treatment was applied after blast, amplitudes recovered to control-like levels. Morphological analysis demonstrated significantly decreased cell counts in all layers after blast but recovered with agonist treatment. Using DAPI stained cells, ONL, INL, and GCL cell counts were significantly decreased after blast exposure in comparison to control conditions. After PNU-282987 treatment following blast, the ONL, INL, and GCL cell counts significantly increased back to control-like levels. In IHC studies, BrdU incorporation was seen in retinal ganglion cells and photoreceptors after PNU-282987 treatment, with or without blast exposure. These are the first experiments to demonstrate neurogenesis in the adult mammalian retina after treatment with an alpha 7 nicotinic acetylcholine receptor agonist. Results of this research may have implications for neurodegenerative diseases, trauma, and aging in adult mammals.
Recommended Citation
Nolasco de Carvalho, Giovanna, "Neurogenic Effects of PNU-282987 Treatment on Blast-Induced Ocular Trauma in Adult Mouse Retinas" (2024). Honors Theses. 3830.
https://scholarworks.wmich.edu/honors_theses/3830
Access Setting
Honors Thesis-Restricted
Restricted to Campus until
6-19-2026