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Xu, Shunbin, PhD

Rush University Medical Center, Chicago, Illinois

Project Title:

Microrna-146 In Diabetic Retinopathy

Grant Number:

7-12-BS-207

Type of Grant:

Basic Science

General Research Subject:

Both Type 1 and Type 2 Diabetes

Project Start Date:

Jul 1, 2012

Project End Date:

Jun 30, 2015

Focus:

Complications, Complications\Ocular, Signal Transduction (Non-Insulin Action), Signal Transduction (Non-Insulin Action)\Cytokines and Apoptosis, Signal Transduction (Non-Insulin Action)\Transcriptional Regulation

Research Description



Diabetic retinal disease (DR) is a leading cause of blindness in the industrialized world. However, there is still no efficient prevention or treatment. Development of new therapy depends on new discoveries of novel mechanisms of genesis of the disease. microRNAs (miRNAs) are newly recognized, small molecules, regulating gene expression and playing important roles in normal development and in various diseases. However, the roles of miRNAs in DR are still utterly unknown. Recently, we identified that one of the miRNAs, miR-146, was increased in the retinal endothelial cells (the lining cells of the retinal blood vessels). We focused on studying retinal endothelial cells besides the retina, because diabetes-induced damages to retinal blood capillaries play pivotal roles in the genesis of DR. More importantly, we discovered that miR-146 can inhibit specific inflammatory response in retinal endothelial cells, therefore, may protect retinal blood vessel cell from cell death and dysfunction caused by diabetes-induced inflammation in the eyes. In this proposal, we will test this hypothesis in diabetic rat models. We will increase the level of miR-146 in retinal endothelial cells by gene delivery method, and test whether increased miR-146 prevents or stops the development of diabetic retinal disease. This research will prove that miR-146 is involved in the genesis of DR, and is a new therapeutic target for the treatment of early DR. Therefore, this research may lead to new drug development for treatment of DR.

Research Profile



What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
Diabetic retinal disease (DR) is a leading cause of blindness in the industrialized world. However, there is still no efficient prevention or treatment. This research focuses on diabetic retinal disease and studies the role of miRNA-146, in diabetic retinal disease and its potential as a therapeutic target for the treatment of diabetic retinal disease. This research will prove that miR-146 is involved in the genesis of DR, and provide proof-of principal evidence that increased expression of miR-146 prevents or stops the development of diabetic retinal disease. Therefore, this research may lead to new drug development for treatment and/or prevention of DR.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Almost all people with type I diabetes and 50-80% of type II diabetic patients will develop diabetic retinal disease, which leads to blindness. Our research will validate a novel therapeutic target for the prevention and treatment of diabetic retinal disease.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Diabetic retinal disease (DR) is a leading cause of blindness in the industrialized world. However, there is still no efficient prevention or treatment. Development of new therapy depends on new discoveries of novel mechanisms of genesis of the disease. microRNAs (miRNAs) are newly recognized, small molecules, regulating gene expression and playing important roles in normal development and in various diseases. However, the roles of miRNAs in DR are still utterly unknown. The ultimate goal of our research is to find better prevention, treatment and cure of DR. This award will allow us to make critical validation of a new therapeutic target and provide proof-of-principle of the therapeutic effect for new drug development.

In what direction do you see the future of diabetes research going?
Development of a comprehensive approach with a combination of accurate early diagnosis, prevention, and patient-specific preventive and therapeutic treatment is the key to the cure of diabetes and diabetic complications. Discovery of novel mechanisms underlying diabetes and diabetic complication and novel therapeutic targets involved in the novel mechanisms will provide breakthrough results and significantly improve the prevention, diagnosis and treatment of diabetes and diabetic complications including diabetic retinal disease.