Novel Pathway May Lead to Proliferative Diabetic Retinopathy Treatment

Diabetic eye disease can lead to formation of abnormal blood vessels in the back of the eye which can lead to vision loss. This is termed proliferative diabetic retinopathy (PDR) and affects up to 40% of those with T1D for more than 20 years. Kazlauskas and colleagues have worked for several years to discover molecules that they term regression factors. These molecules are naturally present in the eye, and help eliminate abnormal blood vessels. In prior work they identified one such factor – lysophosphatidic acid (LPA) which is present normally in the eye and can eliminate abnormal blood vessel growth in various experimental assays. However, this work shows that vessels that develop in the presence of diabetes or high glucose do not have the same response to this protective factor. This work has identified a potential pathway by which this resistance to LPA operates. The investigators show that if they block a certainprotein activity using specific drugs, the protective activity of LPA is restored. This could represent a novel therapeutic strategy to treat PDR in those with diabetes.

Reference:

Aranda J, Motiejunaite R, Im E, Kazlauskas A. Diabetes disrupts the response of retinal endothelial cells to the angiomodulator lysophosphatidic Acid. Diabetes. May 2012;61(5):1225-33.

Ramifications for Individuals with Type 1 Diabetes:

Proliferative diabetic retinopathy is currently treated through laser therapy. This can eliminate growth of abnormal blood vessels in the back of the eye and can help save vision. However, the laser treatment can cause permanent damage to parts of the retina and so alternate therapies that more specifically treat PDR are important. Therapies being developed for diabetic macular edema (DME) such as Lucentis and Eylea may also hold promise for PDR. However, different disease processes occur in DME and PDR, so specific therapies for each may be necessary. This novel pathway contains multiple potential targets for such a therapy which warrant further investigation.

JDRF Involvement:

JDRF funded this work through a regular research grant to Andrius Kazlauskas and a JDRF postdoctoral fellowship to Jorge Aranda.