• National Eye Institute
    Comprehensive Ophthalmology, Neuro-Ophthalmology/Orbit, Retina/Vitreous

    The newly-funded projects are part of the National Eye Institute’s (NEI) Audacious Goals Initiative, a targeted effort to restore vision by regenerating neurons and their connections in the eye and visual system by facilitating cross-disciplinary research.

    “Understanding factors that mediate the regeneration of neurons and the growth of axons is crucial for the development of breakthrough therapies for blinding diseases. What we learn through these projects will have a health impact beyond vision,” said Paul A. Sieving, MD, PhD, director of NEI.

    The six projects include:

    Molecular discovery for optic nerve regeneration

    Jeffrey L. Goldberg, MD, PhD, Andrew D. Huberman, PhD, Stanford University; Larry Benowitz, PhD, Harvard University; Hollis Cline, PhD, Scripps Research Institute

    In this project, researchers hope to identify genes and proteins that help or hinder the ability of retinal ganglion cells to regenerate, grow axons to a target and become functional in mice. Promising molecular candidates will be investigated in longer-term in vivo studies designed to assess changes in  animals’ vision.   

    Screening for molecules that promote photoreceptor synaptogenesis

    Donald J. Zack, MD, PhD, Johns Hopkins University; David Gamm, MD, PhD, University of Wisconsin

    Zack, Gamm and colleagues plan to study precursor photoreceptor cells derived from human stem cells to determine the factors that help coax them into becoming fully developed photoreceptor cells. They hope to identify a list of small molecules and candidate genes that contribute to the ability of photoreceptor cells to home in on their appropriate target cells in the retina, known as bipolar cells.

    Evaluation of novel targets for retinal ganglion cell axon regeneration 

    Stephen M. Strittmatter, MD, PhD, Yale University

    Strittmatter and his team will search for genes that contribute to the regeneration of axons from retinal ganglion cells. Starting with 450 candidate genes, culled from more than 17,000, they will test each candidate in a mouse optic nerve injury model, to see if any act as mediators of regeneration.

    Novel activators of regeneration in Muller glia

    Edward M. Levine, PhD; James G. Patton, PhD; David J. Calkins, PhD, Vanderbilt University

    Levine and his colleagues are investigating exogenous and endogenous factors that contribute to the successful reprogramming of Muller glia, which are supportive cells in the retina. In zebrafish, Muller glia can give rise to photoreceptor cells after injury to the retina. Investigators plan to test a novel combination of pharmacological agents and genetic manipulation for the ability to reprogram Muller glia in mice.

    Comparative transcriptomic and epigenomic analyses of Muller glia reprogramming

    David R. Hyde, PhD, University of Notre Dame; John D. Ash, PhD, University of Florida; Andy J. Fischer, PhD, Ohio State University; Seth Blackshaw, PhD, and Jiang Qian, PhD, Johns Hopkins University

    Hyde and his colleagues are comparing the capacity of Muller glia cells from zebrafish, chicks and mice to shed light on why some species possess the ability to regenerate their damaged retinas while humans cannot. This cross-species comparison will determine what gene activity is upregulated or downregulated, as well as look for epigenomic modifications during retinal development and in response to different forms of retinal damage in animals.

    Novel targets to promote RGC axon regeneration: Insights from unique retinal ganglion cell cohorts

    Kevin Park, PhD; Vance Lemmon, PhD; Sanjoy Bhattacharya, PhD, University of Miami

    Park and Lemmon are using RNA sequencing in cultured retinal ganglion cells to identify differences in the expression of genes in regenerative versus non-regenerative retinal ganglion cells. In parallel, Park and Bhattacharya will use mass spectrometry to determine which lipids (or fat molecules) may give subclasses of retinal ganglion cells more robust regenerative capacities. Furthermore, they will assess the function of the genes found to be involved in regeneration