Exploring the Origins of Diabetic Retinopathy

Diabetic retinopathy is a common occurrence among the patients retina specialist Mira Sachdeva sees at Wilmer Eye Institute, Johns Hopkins Medicine. Despite treatments, it’s a leading cause of blindness for working-age adults.

An assistant professor of ophthalmology and a recent recipient of an endowed Wilmer Rising Professorship, Sachdeva is conducting research to explore diabetic retinopathy’s origins.

Sachdeva, who was chief resident at Wilmer before joining its faculty in 2017, is interested in learning about risks for diabetic retinopathy, why some patients develop different severities of disease, and how changes in the retina can be addressed earlier so it’s possible to prevent progression — or even reverse it if discovered in time.

Much of retinal pathology is irreversible at the time of its discovery, Sachdeva says. “We don’t know much about what’s going on in the retina early in diabetes,” she says. “If we find the earliest dysfunction, that would probably provide a great opportunity to intervene earlier, and maybe detect disease earlier and inform patients about their risks earlier.”

Sachdeva’s research started as a study on how diabetes affects the early inner retinal neurons, specifically the retinal ganglion cells. While she and her team observed visual function changes and retinal thinning in diabetic mice, they did not see a reduction in the number of those cells, as expected.

Sachdeva says it was an unexpected result, but it has opened more opportunities for research on how diabetes may affect the retina and its functionality. “I think, like with a lot of science, sometimes the negative data is maybe more interesting,” she says. Sachdeva and her team have now expanded their lab work to the clinical setting to aid their research.

This includes a clinical project she started last year in which she is studying proteins from eye fluid in patients who have diabetes — but who do not have significant retinopathy — to see if there are factors that might contribute to the understanding of what’s going on in early diabetes. In the works is research in which Sachdeva and her team will look at patients with pre-diabetes and examine if changes are happening in the retina at that stage.

Sachdeva says she and her team hope to find some answers as soon as later this year, including potential leads for specific pathways and cell types that could be involved in how diabetes affects the retina early on.

In the long run, Sachdeva hopes she can find a sign — such as a biomarker that could be detected in the eye — that shows that a patient could be at higher risk for development of diabetic retinopathy, so therapies can be designed to intervene earlier. She also wants a better understanding of how retinal metabolism works.

Being a clinician scientist allows Sachdeva to learn from patients, animal models and cells in parallel, to find new leads and help point her and her team toward the next direction. “I’ve always wanted to include a more clinical and translational arm of my research that complements the basic science,” she says. “Now, I’ve been able to start that.”