Published December 20, 2018
Steven J. Fliesler, PhD, SUNY Distinguished Professor and the Meyer H. Riwchun Endowed Chair Professor of ophthalmology, has been awarded a $2.2 million grant from the National Eye Institute of the National Institutes of Health to better understand a rare cause of blindness that strikes young children.
The grant funds research to use newly created animal models to better understand and eventually treat autosomal recessive retinitis pigmentosa (arRP), a hereditary, progressive and irreversible human blinding disorder. It begins with nighttime vision loss and eventually progresses to total blindness.
The research project targets RP59, a specific type of the disorder, which starts much earlier in childhood than more common forms of the disease.
“As in other forms of RP, the retina’s rod photoreceptor cells — which enable us to see dim light and things without color — deteriorate and die, while the cone photoreceptors — which detect color and are used for visual acuity — are typically unaffected until later in the disease course,” Fliesler says.
“Ours is the first lab to develop a viable and useful mammalian gene ‘knockout’ model of this human genetic disorder,” adds Fliesler, who is also a Research Career Scientist at the VA Western New York Healthcare System.
Discovered in 2011, the genetic defect responsible for RP59 involves a mutation in the gene called DHDDS, a key enzyme required for the synthesis of dolichol, an essential lipid-like molecule.
“Our research will focus on elucidating the molecular mechanism underlying RP59 pathology, by deleting the DHDDS gene selectively in specific cell types in the retina and examining the consequences to retinal structure and function,” says Fliesler, who serves as president of the Association for Research in Vision and Ophthalmology. “Using the knowledge gained from our research, we hope to develop an effective gene therapy to cure or prevent the disease.”
Fliesler — vice-chair and director of research for the Department of Ophthalmology and director of research for the Ira G. Ross Eye Institute Vision Research Center — is an expert in lipid (particularly cholesterol) metabolism in the retina.
He has been funded for more than 30 years by the NIH to conduct pioneering studies into retinal dysfunction and degeneration associated with defects in cholesterol synthesis, such as Smith-Lemli-Opitz syndrome, a rare, often deadly, birth defect. Fliesler also collaborates with colleagues at other institutions on the development of novel gene therapy applications to treat other genetic eye conditions that can lead to incurable blindness.
Steven J. Pittler, PhD, professor in the School of Optometry at the University of Alabama at Birmingham and director of its Vision Science Research Center, is co-principal investigator on the grant.