Title

Neurogenesis of Retinal Neurons in Response to an Alpha 7 Nicotinic Acetylcholine Receptor Agonist

Date of Award

4-2018

Degree Name

Doctor of Philosophy

Department

Biological Sciences

First Advisor

Dr. Cindy Linn

Second Advisor

Dr. Rachel Warga

Third Advisor

Dr. Pamela Hoppe

Fourth Advisor

Dr. David Linn

Abstract

Vision is a sense central to the human condition. Humans, rely on vision to interact with the world around them. As such, impairment or loss of vision due to retinal damage, age or disease, takes a significant toll on individuals, their communities, and healthcare infrastructure. The ability to restore vision that has already been lost would be transformative to the healthcare industry. The current belief is that adult mammals lack the ability to regenerate a meaningful number of retinal neurons. However, this study disagrees with this belief and demonstrates that adult mammals can, in fact, regenerate significant numbers of retinal neurons without damage to the retina, by treatment with the alpha 7 nicotinic acetylcholine receptor agonist, PNU-282987. Treatment with PNU-282987 causes transcriptional changes in a number of molecules shown to be important for regeneration in other vertebrate models and leads to the generation of both new retinal progenitors as well as adult neurons. The new cells are shown to be derived from the resident Müller glia, which are acted upon by the signaling molecules released from the retinal pigment epithelium in response to PNU-282987 treatment. Taken together, these findings demonstrate for the first time that the adult mammalian retina is capable of robust regeneration and neurogenesis, and thus holds great potential and promise for the millions of individuals living with low vision and blindness.

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Dissertation-Abstract Only

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