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ASPIRE Grant Awarded to Study Vision Loss Following Traumatic Brain Injury

ASPIRE Grant Awarded to Study Vision Loss Following Traumatic Brain Injury

Ophthalmology professor Ram Nagaraj, PhD, will lead a multidisciplinary team investigating vision impairment at the molecular level.

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Written by Toni Lapp on August 24, 2022

A $200,000 grant from the University of Colorado School of Medicine's Program to Advance Physician Scientists and Translational Research (CU ASPIRE) will support researchers to develop new, targeted therapies for those who have experienced vision loss following traumatic brain injuries.

More than 2.5 million people in the U.S. sustain traumatic brain injuries, or TBIs, each year, often developing vision impairments, ranging from blurred vision and double vision to irreversible blindness. Vision impairment can occur even in cases of mild TBI, or concussions.

“This could give hope to people experiencing vision loss following a brain injury,” says Ram Nagaraj, PhD, professor of ophthalmology at the Sue Anschutz-Rodgers Eye Center. “We will study what happens to the eye in a TBI. We will look at the retina to see how well it’s functioning – if at all. We know whether light is transmitted to the brain.”

Nagaraj, the principal investigator, has assembled a multidisciplinary team to identify and test treatments to prevent the loss of brain and retinal cells that may become damaged from a TBI. His co-investigators are Alon Poleg-Polsky, MD, PhD, assistant professor of physiology and biophysics, and geneticist Mingxia Huang, PhD, associate professor of dermatology.

Solving the mysteries of TBI-related vision loss

The Sue Anschutz-Rodgers Eye Center sees patients with vision impairments following brain injuries on a weekly basis, as many visual problems result over the course of several weeks following a TBI. A cascade of secondary events may follow the injury, including the loss of stress proteins and the production of inflammatory cytokines, ultimately resulting in the irreversible death of cells in the optic nerve.

Because this degradation can happen quickly, the therapeutic window for treatment is thought to end shortly after the initial trauma. Nagaraj and his team in the CU Department of Ophthalmology hope to identify intervention methods to slow damage to the optic nerve, specifically investigating a therapy in which the eye is injected with a virus containing a protective gene designed to prevent retinal ganglion cell death and suppress cell inflammation in retinas.

Huang will dive deeper into when and where inflammation occurs after a TBI and whether intervention methods may preserve neurons in the retina. This work will also provide insights into when is the optimal time to intervene and how long the window for treatment lasts. Meanwhile, Poleg-Polsky’s team will study which types of cells in the retina die, with a focus on the brain cell receptor N-methyl-D-aspartate, which has played a role in conditions such as Alzheimer’s and Parkinson’s disease.

Fostering research into unmet medical needs

Launched earlier this year, ASPIRE serves as a research incubator to encourage interdisciplinary, programmatic research on CU Anschutz Medical Campus, and ultimately creates research to submit for larger grants from organizations such as the National Institutes of Health.

“These are very prestigious, high-value grants for a university because they help to support this big-science approach to a difficult research problem,” says Mark Petrash, PhD, professor and vice chair for research for the CU Department of Ophthalmology. “This is the way big problems get solved – with multidisciplinary teams.”

Nagaraj’s team is one of four to receive funding in ASPIRE’s inaugural year.

“This project speaks to the vision of department leadership: to provide the resources to the faculty to enable them to take on these high-risk, high-reward projects, and provide the upfront funding to launch that research before external funding is awarded to the project,” Petrash continues.

The initial term of the ASPIRE award is for one year, renewable for a second year, during which the investigators will begin working on a program project grant application. Although Nagaraj’s goal is to one day establish a traumatic brain injury center at the CU Anschutz Medical Campus, the researchers ultimately hope to develop novel treatments that will improve the quality of life for patients who have had brain injuries.

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Ram Nagaraj, PhD

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Mark Petrash, PhD