Singh Awarded $1.9M to Investigate Inflammatory Responses in the Eye That Can Lead to Vision Loss

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Dr. Nikhlesh K. Singh

Retinal neovascularization (RNV) occurs when new blood vessels grow on the surface of the retina. While wound repair in the skin and many other tissues involves neovascularization, in the eye, neovascularization can cause severe vision loss and blindness.

Nikhlesh K. Singh, DVM, PhD, assistant professor in the Department of Physiology in the College of Medicine at the University of Tennessee Health Science Center (UTHSC), was recently awarded $1.9 million from the National Institutes of Health (NIH) to help discover the pathological mechanisms that regulate inflammatory responses in patients with retinal neovascularization, with a goal to develop targeted therapies to preserve their retinal health.

“The development of new therapeutic approaches against retinal neovascularization is limited because of our lack of knowledge about its pathophysiology,” said Dr. Singh. “We know that elevated levels of inflammation and inflammatory mediators have been observed in retinas or in the vitreous body of patients with pathological RNV. We also know that inflammation may exacerbate RNV’s harmful effects. What is unclear is the functional significance of these inflammatory mechanisms and how we can control them.”

Retinal neovascularization is most commonly seen in people suffering from diabetes or macular degeneration, and in premature babies. Intravitreal anti-vascular endothelial growth factor (VEGF) therapy and laser treatments are currently the only treatment options available. However, research shows optimal benefits are not always received by patients who undergo these therapies.

In his preliminary studies, Dr. Singh and his collaborators identified proteins that regulate inflammation. They are now performing further testing on these proteins using a novel approach to determine if manipulating them will lead to successful inflammation regulation, and thus new therapies.

“We have recently identified certain proteins that can specifically block RNV’s in pathological conditions,” said Dr. Singh. “Up until now, these proteins were thought to cause an anti-inflammatory response. Our preliminary data shows that their effects are not only limited to inflammation or inflammatory responses. Our goal is to target those proteins and thereby selectively modulate their abnormal behavior. The outcomes of our study are expected to open up a new line of understanding about the pathophysiology of various proliferative retinopathies.”

Dr. Singh’s project titled, “Cellular Mechanisms of Pathological Retinal Neovascularization,” is being funded for five years.