Diabetic retinopathy (DR) is a leading cause of blindness in the US and one of the major complications of both Type 1 and Type 2 diabetes. Although DR is widely accepted to be an ischemia-driven disease, the current diagnosis and grading of DR severity is based solely on anatomic alterations such as the quantification of abnormal retinal microvasculature in non-proliferative disease or angiogenesis in proliferative stages. As a result, retinal impairment is irreversible in most DR patients when diagnosed, largely due to the lack of technology to quantify retinal ischemia and the lack of knowledge of the underlying mechanism of retinal ischemia. This proposal aims to investigate retinal ischemia in early diabetes using a novel optical coherence tomography technology, which offers the capability to quantify metabolic rate of oxygen (MRO2) in the retina for the first time. We refer to this new technology as visible-light optical coherence tomography or vis-OCT. We seek to identify when MRO2 alterations initially occur, the causes of MRO2 alterations, and whether intervention of MRO2 affects the development of DR in a unique Type 1 mouse model. At the end of the project period, we will have 1) established a time line and mechanistic knowledge of retinal MRO2 changes during the development and progression of DR and 2) fully-optimized the vis-OCT system that is ready to be translated for the next-stage patient testing.

Public Health Relevance

Significant improvement in clinical management of diabetic retinopathy will be possible if it's earliest pathological alterations can be detected and thoroughly understood. Quantitative imaging of retinal oxygen metabolism and comprehensive investigation of pathophysiology of dysfunctional retinal oxygen supply/consumption may provide such a possibility. This project seeks to apply novel, clinically-translatable, functional imaging technology and combine it with longitudinal animal model studies to address these needs.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY026078-02
Application #
9336315
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Greenwell, Thomas
Project Start
2016-09-01
Project End
2021-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
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