Retinal Ganglion Cell Apoptosis is Mediated Through Activation of a7 Nicotinic Acetylcholine Receptors by PNU-282987 and DMP-543 in in-vivo Models of Glaucoma
Littman, Elliott S.
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Glaucoma is a degenerative retinal disease characterized by loss of vision due to the death of retinal ganglion cells (RGCs) in the eyes of mammals. This is primarily caused by buildup of intraocular pressure (IOP) in the eyes triggering the apoptotic pathway of RGCs associated with loss of vision. Most treatments associated with the disease have not yet been shown to practically reduce IOP allowing researchers to examine alternative approaches for treating death of RGCs and consequently glaucoma. Past studies in this lab have shown successful mediation of RGC death through the direct neuroprotective drug treatment of agonist PNU-282987 in an in vivo model of glaucoma. Neuropharmacological drugs like Donepezil and DMP-543 have been shown to influence neuroprotective effects similar to PNU-282987 in-vitro, but have not yet been looked at in-vivo. This study looked at the potential effects of each of these neuropharmacological agent and their targeting mechanisms in RGCs using in-vivo rat models of glaucoma. Rats were given month long eye-drop treatments in their right eyes, given NaCl eye injections to simulate glaucoma conditions induced with glaucoma, sacrificed, and had their retinas harvested and fixed for viewing and analyzing results with an LSM-510 Confocal imaging. Neuroprotection of RGCs was observed in rat models treated with ImM PNU- 282987, 100pM DMP-543, and ImM DMP-543, but not with Donepezil. These results indicate a hopeful step into the future for the preventative treatment of glaucoma and other neurodegenerative diseases.