Ophthalmology Research Grant Funding Reaches 10th Year

This year’s $115,000 grant brings the total awarded to $1,130,000.

The grant primarily supports laboratory-based clinical and translational research. The work includes new projects as well as continuations of current projects.

In 2015, researchers made several key discoveries, resulting in 17 publications in peer-reviewed journals, including Experimental Eye Research, Journal of Diabetes Research and the Proceedings of the National Academy of Sciences.

The grant supported continued studies on the role of the unfolded protein response (UPR) in various disease states that occur in the retina, such as diabetic retinopathy or age-related macular degeneration (AMD).

Sarah X. Zhang, MD, associate professor of ophthalmology, led research studying the role of the UPR in retinal pigment epithelium (RPE) cell death, as initiated by cigarette smoke extract (CSE).

Researchers found CSE-induced UPR was associated with oxidative stress, endoplasmic reticulum stress and mitochondrial damage. These, in turn, resulted in RPE cell death, while also inducing up-regulation of Nrf2, a transcription factor involved in protection against apoptotic cell death.

Zhang found that augmenting the protective potential of transcription factors such as Nrf2 may provide novel therapeutic targets to protect RPE cells from cigarette smoke-associated damage, which has been linked to AMD.

The paper, “Activation of the UPR Protects Against Cigarette Smoke-Induced RPE Apoptosis Through Up-Regulation of Nrf2,” was published in the Journal of Biological Chemistry.

Another UPR-related study led by Zhang was published in Progress in Retinal and Eye Research.

John M. Sullivan, MD, PhD, associate professor of ophthalmology, used grant money to continue his studies of gene therapy approaches to treating retinal degeneration by modifying genetic information, or the messenger RNA, that is produced by the genes.

Researchers in his laboratory developed a novel real-time imaging system to visualize the retina during intraocular gene therapy delivery in mice.

A stereo microscope was converted into an ocular-retinal imaging system, which can be adapted for use during subretinal or intravitreal injections, fluorescence retinal microscopy or real-time fluorescein angiography in mice.

The device potentially will facilitate preclinical gene- or cell-based therapy development in rodent models of human ocular diseases.

The paper, “A Novel, Real-Time, In Vivo Mouse Retinal Imaging System,” was published in Investigative Ophthalmology and Visual Science.

Sangita P. Patel, MD, PhD, assistant professor of ophthalmology, studies the anterior segment of the eye, and in particular, the cornea. The substance of Patel’s research is studying the fundamental mechanisms of how the corneal endothelium helps the cornea keep the normal balance of water and ions at the appropriate levels to maintain its clarity.

In 2015, she investigated the physiologic basis for the toxic effects of amantadine, an anti-Parkinson’s disease drug, on the corneal endothelium.

Patel found that amantadine affected active ion transport in the corneal endothelium, but not by the NMDA receptor-mediated signaling pathway that is the primary mechanism for amantadine’s mode of action in other tissues. Amantadine also caused corneal endothelial cell swelling.

Researchers believe providing a better understanding of the mechanism of amantadine’s effects on the corneal endothelium may facilitate identification of the subset of patients who are at greater risk for susceptibility to amantadine toxicity.

In addition to research, the grant will continue to support two lecture series featuring eminent vision scientists: Distinguished Lectures in Vision Science and Pioneers in Neuroscience.

“These lectures attract some of the most stellar people in ophthalmology and vision science to our campus,” says Steven J. Fliesler, PhD, UB Distinguished Professor and Meyer H. Riwchun Endowed Chair Professor of Ophthalmology, department vice-chair and director of research.

“These events are important for two reasons. One is, of course, we want to hear about their groundbreaking research, what they are doing now and where they are going. It has spawned collaborations between some of our faculty and these visiting scientists,” he says.

“The other very important aspect of these lecture series is to educate people outside of Buffalo that we exist, that we actually have a pretty wonderful setup and group of scientists here,” says Fliesler, who is also a professor of biochemistry.

Visiting speakers come away from their visit impressed that Buffalo has so many benefits, says Fliesler. “It’s an eye opener for them, and that’s important because those are the people who review our grant applications and our papers submitted to journals for peer review and publication.”

A portion of the grant money is also used to facilitate faculty and trainees attending scientific and clinical meetings to present their work.

“We have been very fortunate to have this unrestricted RPB grant, and I am very happy with the productivity of our faculty and the progress we have made in the past year,” Fliesler says. “We are looking to continue building our program, primarily in the areas of stem cell biology, regenerative medicine and gene therapy.”

Fliesler is also a research health scientist with the VA Western New York Healthcare System and director of its vision research center.

As in previous years, James D. Reynolds, MD, professor and chair of the department, is the grant’s designated principal investigator.