UB researcher receives $2.2 million from NIH to study rare disorder causing vision loss in young children

BUFFALO, N.Y. — A University at Buffalo ophthalmology researcher has been awarded a $2.2 million grant from the National Eye Institute of the National Institutes of Health to better understand a rare and devastating cause of blindness that strikes young children.

The purpose of the grant is to utilize newly created animal models to better understand and eventually treat a type of a hereditary, progressive and irreversible human blinding disorder called autosomal recessive retinitis pigmentosa (arRP). It begins with nighttime vision loss and eventually progresses to total blindness.

The grant was awarded to Steven J. Fliesler, PhD, SUNY Distinguished Professor, Meyer H. Riwchun Endowed Chair Professor, vice chair and director of research in the Department of Ophthalmology in the Jacobs School of Medicine and Biomedical Sciences at UB, and his co-principal investigator, Steven J. Pittler, PhD, professor in the School of Optometry at the University of Alabama-Birmingham and director of its Vision Science Research Center.

Their research targets a specific type of the disorder, called RP59, 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 explained.

“Ours is the first lab to develop a viable and useful mammalian gene ‘knockout’ model of this human genetic disorder,” said Fliesler, who also is a professor in the UB Department of Biochemistry and the Neuroscience Graduate Program, as well as a research career scientist at the Veterans Affairs Western New York Healthcare System.

Discovered in 2011, the genetic defect responsible for RP59 involves a mutation in the gene called DHDDS, which is a key enzyme required for the synthesis of an essential lipid-like molecule called dolichol. 

“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,” Fliesler said. “Subsequently, using the knowledge gained from our research, we hope to develop an effective gene therapy to cure or prevent the disease.”

An expert in lipid (particularly cholesterol) metabolism in the retina, Fliesler 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.