The metabolic function of the retinal cells is based on the availability of nutrients and oxygen that are supplied by the chorioretinal circulations. Retinal hypoxia is implicated in the development of major and common blinding human eye diseases, such as, diabetic retinopathy and age-related macular degeneration. However, the relative contribution of the choroidal and retinal vasculatures to the retinal oxygenation in health and disease has not been adequately studied. Moreover, the role of oxygen in the development of retinal diseases, and their associated vascular pathologies, is not well-understood. Therefore, technologies for assessment of retinal oxygenation are greatly needed to broaden knowledge, and thereby advance the available diagnostic and therapeutic procedures for retinal diseases. A method for retinal oxygen tension measurement that utilizes oxygen-sensitive microelectrodes is available, but is invasive and does not have the potential to be clinically applicable. Imaging of intravascular oxygen tension based on phosphorescence emission from an oxygen-sensitive molecular probe has been demonstrated, but with limited depth discrimination. We propose to overcome the limitations of the available techniques by combining our technique of optical section retinal imaging with phosphorescence lifetime imaging to provide noninvasive and quantitative measurements of oxygen tension in the retinal vasculatures and tissue.
The specific aims are to develop and establish a novel imaging system for generating three-dimensional images of oxygen tension in the chorioretinal vasculatures and retinal tissue, to determine normal baselines for spatial and temporal variations in retinal oxygen tension, to obtain and validate retinal oxygen consumption measurements based on phosphorescence images, and to assess inner retinal oxygen consumption by mapping of retinal oxygen tension gradients and vasculature patterns. The proposed studies will provide a foundation for retinal oxygen tension measurements in normal retinas that is necessary for investigating variations in animal models of retinal diseases in the future. Once refined, the technique will serve as a valuable tool for investigating disease-related oxygen dynamics, and thereby, can significantly impact the understanding of the pathophysiology, diagnosis and treatment of retinal diseases.
|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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