Our group studies disease mechanisms in inherited retinal degenerations (IRDs), and evaluates efficacy and safety of potential treatments. IRDs result in vision loss due to mutations in more than 200 different genes and include diagnoses such as Retinitis Pigmentosa, Stargardt Disease, Leber Congenital Amarousis, and others. There are multitudes of different pathological mechanisms resulting from different mutations. Our group uses non-invasive tests to link changes in retinal structure and function to underlying molecular pathology. We also develop and evaluate novel outcome measures for use in clinical trials.
February 22, 2017: Pair of Papers Published in AJO and IOVS
Leber congenital amaurosis (LCA) refers to a group of inherited retinal degenerations caused by mutations in at least 20 different genes. One of the more common LCA genes is GUCY2D encoding the rod and cone phototransduction protein RetGC1. Previous work from our group has shown that patients with GUCY2D-LCA often have near normal retinal structure albeit severe loss of vision. This dramatic dissociation of retinal structure from visual function taken together with successful pre-clinical experiments suggests that GUCY2D-LCA patients are good candidates for gene augmentation therapy. We studied non-conventional outcome measures including full-field sensitivity testing to evaluate rod and cone sensitivity, OCT to evaluate the lack of a foveal bulge, and pupilometry to provide an objective measure of vision. In a subset of patients, we studied multimodal magnetic resonance imaging (MRI) of the brain. They showed relatively intact postgeniculate white matter pathway which was encouraging for the prospect of recovery of visual function with future gene augmentation therapy.
Jacobson SG, CIDECIYAN AV, Sumaroka A, Roman AJ, Charng J, Lu M, Choudhury S, Schwartz SB, Heon E, Fishman GA, Boye SE. Defining outcomes for clinical trials of Leber congenital amaurosis caused by GUCY2D mutations. American Journal of Ophthalmology (in press) 2017. [PubMed]
Aguirre GK, Butt OH, Datta R, Roman AJ, Sumaroka A, Schwartz SB, CIDECIYAN AV, Jacobson SG. Postretinal structure and function in severe congenital photoreceptor blindness caused by mutations in the GUCY2D gene. Investigative Ophthalmology & Visual Science 58:959-973, 2017.
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