Date of Award
Master of Science
Dr. Cindy L. Linn
Dr. Christine Byrd-Jacobs
Dr. John Spitsbergen
Masters Thesis-Campus Only
Previous in-vitro studies have demonstrated that ACh has a neuroprotective effect against glutamate-induced excitotoxicity in retinal ganglion cells (RGCs) through activation of nicotinic ACh receptors (Wehrwein et al., 2004, Thompson et al., 2006, Asomugha et al., 2009). However, any physiological role of ACh as a neuroprotective agent in the intact retina is unknown. To address this issue, we propose to analyze the neuroprotective effect of the ACh agonist, nicotine, in an in-vivo model of glaucoma using adult Long Evans rats.
In these experiments, the left eye in each adult rat was left untreated and used as an internal control. In the right eye, hypertonic saline (0.5 ml of 2 mM NaCl) was injected into the episcleral vein to induce glaucoma (Morrison et al., 1997). After one month, the rats were sacrificed and the retinas were removed, flat mounted, fixed and nuclei were stained with Cresyl Violet. Stained cells in the RGC layer in glaucoma-induced retinas were counted and compared to the number of cells counted in the RGC layer under untreated conditions. This model of glaucoma was used to determine if nicotine could prevent loss of RGCs using an intravitreal injection, eye drops, and transdermal patches, different delivery models.
These results support the hypothesis that hypertonic saline injections into the episcleral vein leads to loss of cells from the RGC layer and can be used as a robust in-vivo model of glaucoma. Results from these studies suggest that nicotine, or other nicotinic agents, could be used in future therapeutic treatment for glaucoma.
Birkholz, "Glaucoma-Induced Cell Loss in the Retinal Ganglion Cell Layer Can Be Prevented Using Nicotine in an In Vivo Rat Model" (2011). Master's Theses. 387.