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2014 Abstracts

Developing a Kinetic Model and Identifying Additional Factors for Müller Cell-Mediated Retinal Regeneration

Christopher Burns, Brigham Young University

Engineering

People around the world suffer from degenerative diseases of the retina that can eventually lead to blindness, including age-related macular degeneration. The human retina does not regenerate spontaneously, increasing the severity and long-term effects of these diseases. Currently, a highly-successful treatment for degenerative diseases of the retina doesn’t exist. Some attempts at retinal regeneration have slowed or stopped degeneration (Lanza). However, restoration of sight to its pre-diseased state requires regeneration of retinal tissue, not simply impedance of degeneration.

Müller cells, a type of retinal glial cell, have been identified as a possible source of cells for retinal regeneration. These cells have the potential to de-differentiate into progenitor cells, which eventually give rise to rod photoreceptors (Gallina, Giannelli). This process is especially efficient and spontaneous in lower vertebrates, including fish. The same level of spontaneous regeneration is not seen in the human retina (Gallina, Giannelli). However, a number of the molecular factors that contribute to the process of retinal neuron regeneration via Müller cells have been identified (Gallina). Our research aims to develop a kinetic model for this process—we hope to identify the combinations, concentrations, and durations of exposure that are crucial for efficient retinal neuron regeneration via Müller cells. We also aim to elucidate what, if any, effect exogenous retinal extracellular matrix (ECM) proteins have on this process, especially the de-differentiation of Müller cells to progenitor cells.

Since Spring term 2013 we have gained experience dissecting bovine eyes, decellularizing whole eyes and eye parts using detergents, and removing the retina from the eye. We are preparing to culture Müller cells from bovine retinas and perform experiments to develop the kinetic model. Ultimately, we hope our work will contribute to the development of a treatment to cure degenerative diseases of the eye by stimulating retinal regeneration.