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.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Greenwell, Thomas
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University of Illinois at Chicago
Schools of Medicine
United States
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Blair, Norman P; Tan, Michael R; Felder, Anthony E et al. (2018) Retinal tissue oxygen tension and consumption during light flicker stimulation in rat. Exp Eye Res 175:207-211
Francis, Andrew W; Wanek, Justin; Shahidi, Mahnaz (2018) Assessment of Global and Local Alterations in Retinal Layer Thickness in Ins2 (Akita) Diabetic Mice by Spectral Domain Optical Coherence Tomography. J Ophthalmol 2018:7253498
Felder, Anthony E; Wanek, Justin; Teng, Pang-Yu et al. (2018) A method for volumetric retinal tissue oxygen tension imaging. Curr Eye Res 43:122-127
Blair, Norman P; Felder, Anthony E; Tan, Michael R et al. (2018) A Model for Graded Retinal Ischemia in Rats. Transl Vis Sci Technol 7:10
Felder, Anthony E; Wanek, Justin; Tan, Michael R et al. (2017) A Method for Combined Retinal Vascular and Tissue Oxygen Tension Imaging. Sci Rep 7:10622
Blair, Norman P; Wanek, Justin; Teng, Pang-yu et al. (2016) The effect of intravitreal vascular endothelial growth factor on inner retinal oxygen delivery and metabolism in rats. Exp Eye Res 143:141-7
Blair, Norman P; Wanek, Justin; Felder, Anthony E et al. (2016) Inner Retinal Oxygen Delivery, Metabolism, and Extraction Fraction in Ins2Akita Diabetic Mice. Invest Ophthalmol Vis Sci 57:5903-5909
Kord Valeshabad, Ali; Wanek, Justin; Zelkha, Ruth et al. (2015) Conjunctival microvascular haemodynamics in sickle cell retinopathy. Acta Ophthalmol 93:e275-80
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
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

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