Areas of Interest
Sight is our most precious sense. Diseases of the retina, like macular degeneration and glaucoma cause blindness and are among the top 10 disabilities affecting people. Macular degeneration results in death of photoreceptors, while glaucoma results in optic nerve degeneration and death of retinal ganglion cells. Although there are a number of approaches to restoring sight to people suffering from these diseases, we think a regenerative approach would be best. Unfortunately, mammals do not normally regenerate retinal neurons or optic axons. However, hope comes from the observation that teleost fish, like zebrafish, have remarkable regenerative abilities and can regenerate a damaged retina and optic nerve. Because the zebrafish and mammalian retina share structure and function, we suspect that mechanisms driving retina and optic nerve regeneration in zebrafish will suggest regenerative strategies that can be applied to mammals.
In the retina of fish and mammals there is only one major glial cell type referred to as a Müller glia. Müller glial cells are traditionally thought to participate in retina structure and homeostasis. We found that in zebrafish, Müller glia respond to retinal injury by undergoing a reprogramming event that endows them with properties of a retinal stem cell. These reprogrammed Müller glia divide to produce a progenitor that amplifies and is capable of regenerating all major retinal neuron types. Using a variety of molecular, genetic, biochemical and cell biological approaches, we have identified and characterized many of the signaling pathways and gene expression programs that underlie Müller glial cell reprogramming and retina regeneration. Similar approaches have been used to study optic nerve regeneration. This information is being used to suggest strategies for stimulating retina and optic nerve regeneration in mammals.
Honors & Awards
Interim Chair, Department of Biological Chemistry, 2015–2018
Bernard W. Agranoff Collegiate Professor of Neuroscience, University of Michigan, 2014
Elected Fellow, American Association for the Advancement of Science, 2014
Innovative Ophthalmic Research Award, Research to Prevent Blindness, 2013
Outstanding Research Mentor Award, Undergraduate Research Opportunity Program, 2010
Research Scientist Recognition Award, University of Michigan, 2003
Wilson Scholar, Wilson Medical Research Foundation, 2001
Discovery Award, Mental Health Research Institute, 1995
Research Scientist Award, University of Michigan, 1994
Vegf signaling between Müller glia and vascular endothelial cells is regulated by immune cells and stimulates retina regeneration.
Mitra S, Devi S, Lee MS, Jui J, Sahu A, Goldman D.
Proc Natl Acad Sci U S A. 2022; 119: e2211690119.
Notch signaling via Hey1 and Id2b regulates Müller glia's regenerative response to retinal injury.
Sahu A, Devi S, Jui J, Goldman D.
Glia. 2021; 69: 2882–98.
Tgfb3 collaborates with PP2A and Notch signaling pathways to inhibit retina regeneration.
Lee M, Wan J, Goldman D.
Elife. 2020; 9: e55137.
Notch Suppression Collaborates with Ascl1 and Lin28 to Unleash a Regenerative Response in Fish Retina, But Not in Mice.
Elsaeidi F, Macpherson P, Mills EA, Jui J, Flannery JG, Goldman D.
J Neurosci. 2018; 38: 2246–61.
Opposing Actions of Fgf8a on Notch Signaling Distinguish Two Müller Glial Cell Populations that Contribute to Retina Growth and Regeneration.
Wan J, Goldman D.
Cell Rep. 2017; 19: 849–62.
Retina regeneration in zebrafish.
Wan J, Goldman D.
Curr Opin Genet Dev. 2016; 40: 41–7.
Zebrafish Müller glia-derived progenitors are multipotent, exhibit proliferative biases and regenerate excess neurons.
Powell C, Cornblath E, Elsaeidi F, Wan J, Goldman D.
Sci Rep. 2016; 6: 24851.
Leptin and IL-6 family cytokines synergize to stimulate Müller glia reprogramming and retina regeneration.
Zhao XF, Wan J, Powell C, Ramachandran R, Myers MG Jr, Goldman D.
Cell Rep. 2014; 9: 272–84.
Retinal injury, growth factors, and cytokines converge on β-catenin and pStat3 signaling to stimulate retina regeneration.
Wan J, Zhao XF, Vojtek A, Goldman D.
Cell Rep. 2014; 9: 285–97.
Zinc-binding domain-dependent, deaminase-independent actions of apolipoprotein B mRNA-editing enzyme, catalytic polypeptide 2 (Apobec2), mediate its effect on zebrafish retina regeneration.
Powell C, Cornblath E, Goldman D.
J Biol Chem. 2014; 289: 28924–41.
For a list of publications from MyNCBI, click HERE