The retinal tissue requires an adequate supply of oxygen and nutrients to maintain normal metabolism and function. Insufficient blood flow (ischemia) leads to reduced tissue oxygenation (hypoxia), development of pathologies, and ultimately tissue loss. Hypoxia-triggered pathologies can cause visual impairment in many retinal diseases, including vascular occlusions, diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, and glaucoma. Several factors, including vascular malperfusion, oxygen supply to demand adequacy, tissue hypoxia, and impaired energy metabolism contribute to vision loss. In order to gain knowledge of the relation among these factors, measurements of retinal oxygen delivery, oxygen extraction fraction, tissue oxygen tension and oxygen metabolism are required. Indeed, a combined and correlative evaluation of these key retinal oxygen metabolic-related parameters (oxygen delivery, oxygen extraction fraction, tissue oxygen tension, oxygen metabolism) is essential to understand the role of oxygen deficiency in the development of vision-threatening pathologies. The objective of the research project is to advance knowledge of retinal disease pathophysiology by a comprehensive and innovative investigation of retinal oxygen dynamics with the use of novel imaging technologies.
The specific aims are to: 1) identify retinal oxygen metabolic-related parameters measured immediately after ischemia that can predict subsequent tissue outcomes; 2) elucidate compensatory capacities and consequent susceptibility of diabetic retina to impaired oxygen metabolism; 3) establish a threshold for retinal tissue injury based on the relation of the level and duration of ischemia to subsequent tissue outcomes; 4) determine alterations in edematous retinal tissue oxygenation and its response to light flicker-induced increased metabolic activity. The findings will impact the field by identifying clinically translatable markers to improve diagnostic/prognostic evaluation of retinal vascular occlusions, diabetic retinopathy and macular edema, as well as, propel development of preventative/therapeutic procedures that can successfully combat vision loss, thus improving the quality of life and reducing the cost of caring for the visually impaired.

Public Health Relevance

Retinal hypoxia is implicated in the development of pathologies that cause visual impairment due to major and common retinal diseases, such as retinal vascular occlusions, diabetic retinopathy and age-related macular degeneration. A comprehensive investigation of retinal oxygen dynamics is necessary to understand the role of oxygen deficiency in the development of vision-threatening pathologies. The findings will advance knowledge of pathophysiology of retinal diseases that is essential for devising treatments for restoration of vision and prevention of vision to improve the quality of life and reduce the cost of caring for the visually impaired.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY017918-11A1
Application #
9469370
Study Section
Diseases and Pathophysiology of the Visual System Study Section (DPVS)
Program Officer
Shen, Grace L
Project Start
2007-09-01
Project End
2023-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
11
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Southern California
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90033
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
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
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
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; Gaynes, Bruce; Lim, Jennifer I et al. (2013) Human bulbar conjunctival hemodynamics in hemoglobin SS and SC disease. Am J Hematol 88:661-4

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