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 #
5R01EY017918-14
Application #
10090466
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
2021-02-01
Budget End
2022-01-31
Support Year
14
Fiscal Year
2021
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
90089
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
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

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