News & Research

    Schepens Eye Research Institute, Boston, Massachusetts

The Effect of Chronic Hyperglycemia on Retinal Vascular Regression

General Research Subject: Both Type 1 And Type 2 Diabetes

Focus: Complications\Ocular, Signal Transduction (Non-Insulin Action)\Phosphatases-Kinases

Type of Grant: Mentor Based Minority Postdoctoral Fellowship

Project Start Date: July 1, 2009

Project End Date: June 30, 2012

Research Description

The hyperglycemia associated with diabetes disrupts vascular homeostasis on diabetic patients, facilitating the development of multiple complications. Among these, diabetic retinopathy (DR) is one of the most frequent, and a leading cause of blindness. The first stage of DR is characterized by the loss of retinal blood vessels and a decrease of retinal oxygenation. This leads to a second phase, characterized by the erratic growth of neo-vessels that invade the vitreous humor remaining there for prolonged periods of time. This condition can eventually produce blindness. The objective of this proposal is to elucidate the mechanisms behind hyperglycemia-mediated disruption of retinal vascular homeostasis. To do this, an in vitro model were retinal endothelial cells are stimulated to form tubes was used.

The tubes regressed within a day. It has been described that this regression is a deliberate pathway engaged by the enzyme autotaxin (ATX) and its product, the regression factor lysophosphatidic acid (LPA). Preliminary experiments show that tubes derived from vascular cells exposed to chronic high glucose (HG) conditions from tubes normally, but do not engage regression. Our working hypothesis is that hyperglycemia prevents tube regression by reducing ATX production, inhibiting its activity and/or blunting the responsiveness to LPA. Current knowledge proposes that DR initiation and evolution are the result of increased angiogenic factors. Preliminary data suggests that inhibition of vascular regression pathways also contributes to DR. Finding that hyperglycemia alters the vascular regression program would be a conceptual breakthrough in understanding how diabetes impacts vascular homeostasis.

Reseacher Profile

Mentor: Andrius Kazlauskas, PhD   Postdoctoral Fellow: Jorge Aranda, PhD

What area of diabetes research does your project cover?  What role will this particular project play in preventing, treating and/or curing diabetes? 

Our project focuses on the area of diabetic complications with a particular emphasis on how diabetes deregulates angiogenesis and leads to proliferative diabetic retinopathy (PDR).  The insights we gain regarding how diabetes impacts vascular homeostasis will provide the conceptual foundation necessary to develop novel approaches to prevent diabetic complications such as PDR, and to improve treatment options for the existing population of patients with PDR. 

If a person with diabetes were to ask you how your project will help them in the future, how would you respond? 

The goal of this project is to learn how diabetes upsets vascular homeostasis.  This information will guide development of new ways to prevent and manage diabetic complications. 

Why is it important for you, personally, to become involved in diabetes research?  What role will this award play in your research efforts? 

It is important to become involved in diabetes research for two reasons.  Firstly, diabetic complications constitute an opportunity to study the mechanistic underpinnings of pathological angiogenesis.  Secondly, our findings will lead to improved approaches to prevent and manage diabetic complications, and thereby improve the quality of life for persons afflicted by diabetes. 

In what direction do you see the future of diabetes research going? 

Basic research is a proven approach to guide development of new therapeutic options.  For instance, the development of Imatinib (an inhibitor of key enzymes responsible for signal transduction) to treat patients with chronic myelogenous leukemia, and anti-VEGF therapies that have been an outstanding advance for ocular angiopathies such as PDR and wet age-related macular degeneration.  Thus the future of diabetes research is in basic studies and translating them to new therapeutic options.