The metabolic function of cells in the inner retina relies on the availability of nutrients and oxygen that are supplied by the retinal circulation. Iner retinal hypoxia is implicated in common and blinding human eye diseases, such as diabetic retinopathy and retinal vascular occlusions. However, the role of oxygen in the development of vascular pathologies is still not completely understood. For a complete assessment of inner retinal tissue vitality, knowledge of vascular and tissue oxygen content, blood flow, and metabolic rate of oxygen is required. Additionally, mapping of retinal oxygenation is necessary for identification of localized pathological abnormalities in a comprehensive manner. Studies performed thus far have not measured these parameters together or over extended retinal areas. Therefore, there is limited knowledge of the interplay among vascular malperfusion, tissue hypoxia, and energy metabolism impairment due to retinal ischemic conditions. The objective of the research proposal is to provide a comprehensive study of oxygen dynamics in the inner retina under normal and challenged physiological conditions, and experimental ischemic states. The study will be possible with the use of our novel retinal vascular and tissue oxygen tension (PO2) mapping technique coupled with blood flow measurements.
The specific aims are to: 1) determine abnormalities in retinal vascular PO2, gradients of microvascular PO2, and inner retina oxygen extraction fraction in experimental diabetes, 2) develop a novel imaging system for simultaneous measurements of retinal vascular PO2 and blood flow, and derive measurements of inner retinal metabolic rate of oxygen (MO2), 3) determine normal responses of retinal blood flow, inner retinal MO2 and tissue PO2 to visual stimulation by light flicker, and 4) map the spatial distribution and degrees of retinal hypoxia in experimental diabetes and retinal arterial occlusion. The findings will impact the field by broadening knowledge of coupling between retinal blood flow and oxidative metabolism under a normal physiological condition and elucidate retinal oxygen dynamics in the pathogenesis of diabetic retinopathy and retinal vascular occlusions.

Public Health Relevance

Retinal hypoxia is implicated in the development of major and common blinding human eye diseases, such as diabetic retinopathy. A better understanding of retinal oxygen dynamics is greatly needed to advance the available diagnostic and therapeutic procedures for retinal ischemic diseases. The proposed research will provide a complete study of retinal oxygen dynamics under normal, physiologically altered, and experimentally induced pathologic conditions. The findings of the study will enable future assessment of therapies for diabetic retinopathy (vitrectomy and laser treatment) and emerging therapeutic interventions (anti-VEGF and corticosteroids), to increase their effectiveness by more timely application.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY017918-06
Application #
8487407
Study Section
Special Emphasis Panel (ZRG1-NT-L (09))
Program Officer
Shen, Grace L
Project Start
2006-12-01
Project End
2017-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
6
Fiscal Year
2013
Total Cost
$378,813
Indirect Cost
$141,313
Name
University of Illinois at Chicago
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Kord Valeshabad, Ali; Wanek, Justin; Zelkha, Ruth et al. (2015) Conjunctival microvascular haemodynamics in sickle cell retinopathy. Acta Ophthalmol 93:e275-80
Mezu-Ndubuisi, Olachi J; Wanek, Justin; Chau, Felix Y et al. (2014) Correspondence of retinal thinning and vasculopathy in mice with oxygen-induced retinopathy. Exp Eye Res 122:119-22
Moss, Heather E; Treadwell, Gillian; Wanek, Justin et al. (2014) Retinal vessel diameter assessment in papilledema by semi-automated analysis of SLO images: feasibility and reliability. Invest Ophthalmol Vis Sci 55:2049-54
Teng, Pang-yu; Wanek, Justin; Blair, Norman P et al. (2014) Response of inner retinal oxygen extraction fraction to light flicker under normoxia and hypoxia in rat. Invest Ophthalmol Vis Sci 55:6055-8
Wanek, Justin; Teng, Pang-Yu; Blair, Norman P et al. (2014) Inner retinal oxygen delivery and metabolism in streptozotocin diabetic rats. Invest Ophthalmol Vis Sci 55:1588-93
Teng, Pang-yu; Wanek, Justin; Blair, Norman P et al. (2013) Inner retinal oxygen extraction fraction in rat. Invest Ophthalmol Vis Sci 54:647-51
Wanek, Justin; Gaynes, Bruce; Lim, Jennifer I et al. (2013) Human bulbar conjunctival hemodynamics in hemoglobin SS and SC disease. Am J Hematol 88:661-4
Mezu-Ndubuisi, Olachi J; Teng, Pang-yu; Wanek, Justin et al. (2013) In vivo retinal vascular oxygen tension imaging and fluorescein angiography in the mouse model of oxygen-induced retinopathy. Invest Ophthalmol Vis Sci 54:6968-72
Wanek, Justin; Teng, Pang-Yu; Blair, Norman P et al. (2013) Inner retinal oxygen delivery and metabolism under normoxia and hypoxia in rat. Invest Ophthalmol Vis Sci 54:5012-9
Wanek, Justin; Blair, Norman P; Shahidi, Mahnaz (2012) Outer retinal oxygen consumption of rat by phosphorescence lifetime imaging. Curr Eye Res 37:132-7

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