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Researchers identify candidate biomarker of accelerated onset diabetic retinopathy

April 01, 2016

(BOSTON) - Researchers from Massachusetts Eye and Ear and Schepens Eye Research Institute have shown an association between a defective myogenic response -- the regulatory increase or decrease in blood pressure to keep blood flow within the vessels of the retina constant -- and early, accelerated development of retinopathy in patients with type 1 diabetes. These findings, published online today in Investigative Ophthalmology and Visual Science, identify one mechanism to explain why some patients develop diabetic retinopathy sooner than others. Furthermore, the findings provide a target for future study, which may lead to therapies to delay or prevent the development of accelerated onset diabetic retinopathy.

"In patients with a normal myogenic response, the retinal vessels constrict when increased pressure arrives, to maintain constant blood flow and avoid damage to the smaller vessels in the retina," said Mara Lorenzi, M.D., senior scientist at Massachusetts Eye and Ear/Schepens Eye Research Institute and a professor of ophthalmology, part-time at Harvard Medical School. "But we saw that, in about half of the diabetic patients in our study, the vessels did not constrict. In fact, paradoxically, some patients' vessels dilated, and the blood flow to the retina was increased. This becomes a mechanism of damage for the small vessels, because these tiny, delicate capillaries are exposed to a big flow of pressure that can lead to the little hemorrhages and fluid leakage that are characteristic of diabetic retinopathy."

The study included a small prospective study, in which the researchers closely followed 17 patients with type 1 diabetes whose myogenic responses had been measured four years prior. In approximately half of those patients, the researchers had observed defective myogenic responses. Five out of seven patients with defective myogenic responses developed accelerated diabetic retinopathy. The study also included a different group of patients with type 1 diabetes who had just developed retinopathy. Among these patients, the defective myogenic response was found only in those in whom retinopathy had appeared after a short duration of diabetes (fewer than 15 years of diabetes).

The most common diabetic eye disease and a leading cause of blindness in American adults, diabetic retinopathy occurs when blood vessels in the retina become damaged and leak fluid. Accumulation of fluid into the retina can lead to macular edema . As the damage due to diabetes progresses, the vessels become occluded and can no longer carry blood. New blood vessels grow on the surface of the retina (proliferative retinopathy); but the new vessels are immature and may rupture impairing vision.. Loss of visual acuity as a result of diabetic retinopathy is often the first warning sign for patients yet to be diagnosed with type 2 diabetes.

Currently, there are no treatments for diabetic retinopathy beyond controlling blood sugar and blood pressure levels. The new vessels of proliferative retinopathy can be treated with laser techniques, often at the expense of a portion of the retina. With the knowledge gained from the new studies, the researchers hope to target the defective myogenic response and develop therapies to prevent the development of accelerated diabetic retinopathy in this population. A larger study is needed to test the predictive capability of this abnormality.

"Now, we have a target to be investigated for the development of drugs or interventions to halt or stall the onset of clinical retinopathy," Dr. Lorenzi said.
-end-
Authors on the Investigative Ophthalmology and Visual Science paper include last author Mara Lorenzi, M.D., first author Francesco Tecilazich, M.D., Gilbert T. Feke, Ph.D., Sara Mazzantini, M.D., and Lucia Sobrin, M.D., MPH, of Massachusetts Eye and Ear.

This research study was supported by the OneSight Research Foundation and Schepens Eye Research Institute.

About Massachusetts Eye and Ear

Mass. Eye and Ear clinicians and scientists are driven by a mission to find cures for blindness, deafness and diseases of the head and neck. Now united with Schepens Eye Research Institute, Mass. Eye and Ear is the world's largest vision and hearing research center, developing new treatments and cures through discovery and innovation. Mass. Eye and Ear is a Harvard Medical School teaching hospital and trains future medical leaders in ophthalmology and otolaryngology, through residency as well as clinical and research fellowships. Internationally acclaimed since its founding in 1824, Mass. Eye and Ear employs full-time, board-certified physicians who offer high-quality and affordable specialty care that ranges from the routine to the very complex. U.S. News & World Report's "Best Hospitals Survey" has consistently ranked the Mass. Eye and Ear Departments of Otolaryngology and Ophthalmology as top in the nation. For more information about life-changing care and research, or to learn how you can help, please visit MassEyeAndEar.org.

About Harvard Medical School Department of Ophthalmology

The Harvard Medical School (HMS) Department of Ophthalmology (eye.hms.harvard.edu) is one of the leading and largest academic departments of ophthalmology in the nation. More than 350 full-time faculty and trainees work at nine HMS affiliate institutions, including Massachusetts Eye and Ear, Schepens Eye Research Institute of Massachusetts Eye and Ear, Massachusetts General Hospital, Brigham and Women's Hospital, Boston Children's Hospital, Beth Israel Deaconess Medical Center, Joslin Diabetes Center/Beetham Eye Institute, Veterans Affairs Boston Healthcare System, VA Maine Healthcare System, and Cambridge Health Alliance. Formally established in 1871, the department has been built upon a strong and rich foundation in medical education, research, and clinical care. Through the years, faculty and alumni have profoundly influenced ophthalmic science, medicine, and literature--helping to transform the field of ophthalmology from a branch of surgery into an independent medical specialty at the forefront of science.

Massachusetts Eye and Ear Infirmary

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