Study finds common transcription factor that may be key to reduced retinopathy

New therapeutic target could reduce diabetic retinopathy

Laser treatments or intravitreal injections could be a thing of the past when it comes to treating proliferative diabetic retinopathy (PDR) if findings from new research into retinal neovascularization are any indication.

Published online in the journal Diabetes, the Massachusetts Eye and Ear Infirmary study identifies a particular transcription factor commonly found in abnormal retinal blood vessels that can be inhibited to achieve a 50 percent reduction in retinopathy. Such results could prove promising for the leading cause of new blindness or low vision among American adults.

I want people with diabetes to continue to do what works: adhere to good diabetes self-care, including annual, dilated, comprehensive eye examinations.

PDR, the most advanced stage of diabetic retinopathy, occurs with retinal neovascularization that can result in serious vision loss or blindness. Catching diabetic retinopathy early enough is critical to preserving vision, but this study hints at going beyond early detection-the possibility of using self-administered topical eye drops or systemic drugs to hedge against neovascularization in the first place.

Per the report, researchers studied PDR patients' fibrovascular membrane tissue and identified the presence of the transcription factor RUNX1 expressed in response to high glucose. When RUNX1 activity was inhibited by a small molecule cancer drug, researchers noted a significant reduction in abnormal blood vessels.

Although these results were observed in preclinical models, study authors hope to continue this research, including whether such drugs could be delivered topically versus via injection, and how RUNX1 and vascular endothelial growth factor (VEGF) interplay in angiogenesis. 

"Current treatments to control retinal neovascularization require injecting very large proteins, including antibodies, into the eyes of patients as often as once a month," notes co-corresponding author Joseph Arboleda-Velasquez, M.D., Ph.D., in a study news release. "Our study opens the door for novel modalities of treatment based on small molecules that could cross biological barriers on their own. Such a treatment could be self-administered by patients and eliminate the need for intravitreal injections." 

The study was supported with grants from the National Institutes of Health.

 Cautiously optimistic

Although this study could point to a significant development in diabetes care, Tina MacDonald, O.D., C.D.E., stresses that such developments were studied in vitro and in mice models. Nonetheless, if a 50 percent reduction in retinopathy were to translate in humans, "that could stamp out much of blindness due to diabetes," she says.

"For all the similarities humans have with mice, more needs to be done before we declare this 'manna from heaven,'" Dr. MacDonald says. "I want people with diabetes to continue to do what works: adhere to good diabetes self-care, including annual, dilated, comprehensive eye examinations. And we will all be watching this development very closely."

It's estimated that nearly 29 million Americans-9 percent of the population-had diabetes in 2012 with another 1.4 million Americans diagnosed every year. But not all are aware of their condition. About 8 million Americans go undiagnosed, representing an at-risk population that optometry is crucially poised to help. 

Doctors of optometry are often the first health care practitioners to examine persons with undiagnosed diabetes or ocular manifestations of diabetes. In 2014 alone, doctors of optometry diagnosed 240,000 patients with diabetes. That's because telltale vascular changes are detectable via a routine comprehensive eye examination, allowing for swift referral into appropriate care. Once established with a multidisciplinary diabetes care team, regular dilated eye examinations with an eye doctor are critical to preserving vision and reducing the risk of vision loss.  

The AOA's first, evidence-based clinical practice guideline, Eye Care of the Patient with Diabetes Mellitus, not only offers doctors a vital resource for diabetes care, but also provides optometry with substantial evidence to support professional advocacy. In the interest of providing quality, relevant clinical care information, the diabetes guideline is now undergoing a scheduled review per Institute of Medicine guideline development standards.  

Read more about how optometry is redefining its role in diabetes care in the November/December 2016 edition of AOA Focus (member login required).

May 8, 2017

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