National Glaucoma Research - Completed Award

	Daniel Goldman, Ph.D. The Regents of the University of Michigan Ann Arbor, MI Title: Müller glia-dependent regeneration of retinal ganglion cells Non-Technical Title: Retinal ganglion cell regeneration for retinal repair Acknowledgements: Recipient of the Thomas R. Lee award for National Glaucoma Research Duration: April 1, 2010 - March 31, 2012 Award Type: Standard Award Amount: $100,000
Summary: This research aims to test the hypothesis that retinal ganglion cell death stimulates “Müller glia” dedifferentiation into a population of proliferating retinal progenitors that can regenerate lost retinal ganglion cells. We propose to use zebrafish in these studies because of their robust regenerative powers. Our approach is to first generate a transgenic zebrafish model of retinal ganglion cell death, similar to that which occurs during glaucoma, and then investigate if Müller glia can regenerate these damaged cells.

Details:

My lab is interested in identifying strategies for repairing the diseased and injured retina. We are focusing on endogenous mechanisms of retinal repair and are investigating if Müller glia, which are resident to the retina, can be coaxed to regenerate damaged retinal ganglion cells. If we can stimulate Müller glia to regenerate retinal ganglion cells it may provide a means for restoring retinal ganglion cell function in diseases like glaucoma. We use zebrafish as a model system for these studies because they exhibit a very robust regenerative response to retinal injury which helps in identifying mechanisms underlying successful regeneration. Although we know that Müller glia can function as retinal stem cells following injury, no one has tested whether damage specifically targeted to retinal ganglion cells, as occurs in glaucoma, is sufficient to stimulate Müller glia-dependent retinal ganglion cell regeneration. We propose to develop a new zebrafish model to test this idea and then use this model to uncover the molecular mechanisms underlying Müller glia-dependent retinal ganglion cell regeneration. We anticipate that these mechanisms will suggest novel strategies for stimulating Müller glia to repair damaged retinal ganglion cells following injury or disease of the human retina.

Publications:

Wan, J., Ramachandran, R. and Goldman, D. HB-EGF is necessary and sufficient for Muller glia dedifferentiation and retina regeneration. Dev Cell, 2012; 22:334-347.