Impairments of retinal hemodynamics and oxygen metrics in ocular hypertension-induced ischemia-reperfusion

Abstract

Ischemia-reperfusion (I/R) is an established model for retinal neurodegeneration. However, there is limited knowledge of retinal physiological metrics and their relationships to retinal function and morphology in the I/R model. The purpose of the study was to test the hypotheses that retinal hemodynamic and oxygen metrics are impaired and associated with visual dysfunction, retinal thinning, and retinal ganglion cell (RGC) loss due to I/R injury. Intraocular pressure (IOP) was increased in one eye of 10 rats for 90 min followed by reperfusion. Fellow eyes served as controls. After one week of reperfusion, multimodal imaging was performed to quantify total retinal blood flow (TRBF) and retinal vascular oxygen contents. Retinal oxygen delivery (DO₂) and metabolism (MO₂) were calculated. Pattern-evoked electroretinography (PERG) and optical coherence tomography were performed to measure RGC function and retinal thicknesses, respectively. RGCs were counted from retina whole mounts. After one week of reperfusion, TRBF was lower in study eyes than in control eyes (p < 0.0003). Similarly, DO₂ and MO₂ were reduced in study eyes compared to control eyes (p < 0.003). PERG amplitude, TRT, IRT, ORT, and RGCs were also lower in study eyes (p ≤ 0.01). DO₂ and MO₂ were correlated with PERG amplitude, TRT, IRT, and ORT (r ≥ 0.6, p ≤ 0.005). The findings improve knowledge of physiological metrics affected by I/R injury and have the potential for identifying biomarkers of injury and outcomes for evaluating experimental treatments.

Keywords: Blood flow; Ischemia-reperfusion; Oxygen delivery; Oxygen metabolism; Retinal thickness; Visual function.

Figure 1:

Comparison of (A) arterial diameter, (B) venous diameter, (C) venous blood velocity, and (D) total retinal blood flow (TRBF) between control and study eyes. Error bars indicate standard deviations. Asterisks indicate significance at P ≤ 0.05.

Figure 2:

Comparison of (A) oxygen delivery (DO₂), (B) oxygen metabolism (MO₂), and (C) oxygen extraction fraction (OEF) between control and study eyes. Error bars indicate standard deviations. Asterisks indicate significance at P ≤0.05.

Figure 3:

Comparison of pattern-evoked electroretinography amplitude between control and study eyes. Error bars indicate standard deviations. Asterisks denote a significant difference at p ≤ 0.05.

Figure 4:

Comparison of (A) total retinal thickness (TRT), inner retinal thickness (IRT), and outer retinal thickness (ORT), and (B) the number of retinal ganglion cells (RGCs) between control and study eyes. (C) The relationship between IRT and the number of RGCs based on compiled data from both eyes. Error bars indicate standard deviations. Asterisks denote a significant difference at p ≤ 0.05.

Figure 5:

Relationships of oxygen delivery (DO₂) and oxygen metabolism (MO₂) with (A) pattern-evoked electroretinography amplitude, (B) total retinal thickness (TRT), and (C) inner retinal thickness (IRT).