Retinal Hypoxia: Relation to Blood Flow and Oxygen Metabolic Biomarkers.

Abstract

PURPOSE: Reduced inner retinal tissue PO2 (tPO2) from reduced total retinal blood flow (TRBF) often causes visual loss. We tested the hypotheses that, in ischemia, (1) tPO2 is linearly related to TRBF and delivery rate of oxygen to the retinal circulation (DO2), and (2) the relationships of tPO2 with the oxygen extraction fraction (OEF) and rate of inner retinal oxygen metabolism (MO2) are nonlinear. METHODS: The study was performed in 32 rats under either normal condition or a wide range of retinal ischemia induced by ipsilateral or bilateral common carotid artery occlusion. The tPO2 and TRBF were determined by multimodal imaging. We also included TRBF, DO2, OEF, and MO2 data in 25 rats from our previous studies using identical methods, but without tPO2 measurements. RESULTS: The tPO2 was linearly related to TRBF (R2 = 0.86). Based on tPO2 derived from TRBF, tPO2 was linearly related to DO2 (R2 = 0.97). OEF was related to tPO2 by a sigmoid function (R2 = 0.97). A critical tPO2, 6.20 millimeters of mercury (mm Hg), was derived below which OEF = unity and MO2 decreases linearly (phase 1). Above this value, OEF <1 and MO2 increased as a function of tPO2 (phase 2) according to Michaelis-Menten kinetics (R2 = 0.73). CONCLUSIONS: During graded retinal ischemia, we showed a linear relationship between tPO2 both TRBF and DO2. A critical tPO2 value defined the nonlinear biphasic relationships of OEF and MO2 with tPO2. The relationships of these biomarkers show promise for advancing knowledge of retinal ischemia and hypoxia.