GDNF Family Ligands in Retinal Development and Survival

Milam A. Brantley Jr, M.D., Ph.D.

DEPARTMENT OF Ophthalmology & Visual Science
Keywords: retinal degeneration, GDNF, ocular electrophysiology

My laboratory’s long-term goals are to develop a better molecular understanding of photoreceptor cell death in retinal degenerative diseases, and to use this information to develop novel treatments for these conditions.

Photoreceptor cell death is the final, irreversible step in the progression of blinding diseases such as retinitis pigmentosa and age-related macular degeneration. Limited treatment options are available for individuals with these conditions. One therapeutic strategy seeks to provide neurotrophic factors to diseased retina in an effort to prolong photoreceptor cell survival. The GDNF family ligands (GFLs) in conjunction with their respective GDNF family receptors (GFRas), activate intracellular signaling through the Ret tyrosine kinase. These factors are potent survival factors for dopaminergic, sympathetic, and parasympathetic neurons. Members of the GDNF family have been localized to the retina, and may play important roles in retinal development and maintenance.

My current research aims include using immunohistochemistry with wild type and reporter knock-in mice to determine the spatial and temporal expression patterns of GDNF family members in the normal murine retina. I am also exploring the retinal phenotype produced by loss-of-function mutations in the GFLs, GFRas, and Ret using histopathology to examine morphology and ocular electroretinography and visual evoked response to evaluate retinal function. We will also investigate whether gain-of-function mutations in GFLs or virally-mediated addition of GFLs can slow photoreceptor cell death in mice with retinal degeneration.

In addition to these studies, I am interested in developing better ocular electrophysiology techniques to study retinal function in attractive mouse mutants.

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