Blood Pressure Modifies Retinal Susceptibility to Intraocular Pressure Elevation

Abstract

Primary open angle glaucoma affects more than 67 million people. Elevated intraocular pressure (IOP) is a risk factor for glaucoma and may reduce nutrient availability by decreasing ocular perfusion pressure (OPP). An interaction between arterial blood pressure and IOP determines OPP; but the exact contribution that these factors have for retinal function is not fully understood. Here we sought to determine how acute modifications of arterial pressure will affect the susceptibility of neuronal function and blood flow to IOP challenge. Anaesthetized (ketamine:xylazine) Long-Evan rats with low (∼60 mmHg, sodium nitroprusside infusion), moderate (∼100 mmHg, saline), or high levels (∼160 mmHg, angiotensin II) of mean arterial pressure (MAP, n = 5–10 per group) were subjected to IOP challenge (10–120 mmHg, 5 mmHg steps every 3 minutes). Electroretinograms were measured at each IOP step to assess bipolar cell (b-wave) and inner retinal function (scotopic threshold response or STR). Ocular blood flow was measured using laser-Doppler flowmetry in groups with similar MAP level and the same IOP challenge protocol. Both b-wave and STR amplitudes decreased with IOP elevation. Retinal function was less susceptible to IOP challenge when MAP was high, whereas the converse was true for low MAP. Consistent with the effects on retinal function, higher IOP was needed to attenuated ocular blood flow in animals with higher MAP. The susceptibility of retinal function to IOP challenge can be ameliorated by acute high BP, and exacerbated by low BP. This is partially mediated by modifications in ocular blood flow.

Evaluation of the effect of elevated intraocular pressure and reduced ocular perfusion pressure on retinal capillary bed filling and total retinal blood flow in rats by OMAG/OCT

“…Increased IOP therefore has a greater impact upon retinal capillary filling in animals with lower MAP, consistent with the observations of He et al (2012). This suggests that OPP is the principal determinant of blood flow change rather than IOP itself.…”

“…Liang et al (2009a) showed that elevated IOP reduced blood flow in the optic nerve head of non-human primates only when systemic blood pressure was reduced. He et al (2012) also demonstrated this effect at a functional level. They showed that retinal ganglion cell function, as determined by the scotopic threshold response (STR) of the electroretinogram, was less susceptible to an IOP challenge with high MAP compared to low MAP.…”

“…More recently, 90 minute variations were shown to not produce permanent ERG changes unless the IOP was higher than 60 mm Hg (Bui et al, 2013). However, analysis of ocular blood flow indicates that retinal blood flow is more sensitive, demonstrating a reduction to well below 50% of baseline at this level of pressure (He et al, 2012; Zhi et al, 2012a). He and colleagues have proposed that retinal function is maintained in the face of this reduced total blood flow by a compensatory increase in oxygen extraction (He et al, 2013).…”

Optic Nerve Head Blood Flow Response to Reduced Ocular Perfusion Pressure by Alteration of Either the Blood Pressure or Intraocular Pressure

“…35 By measuring both retinal function and ocular BF in rats, higher BP has been found to have a protective effect on retinal function and this has been considered to be mediated by improved BF. 36 Collectively, despite differences in tissues, species and experimental conditions, these earlier results and the current results suggest that higher BP enhances BF autoregulation and lower BP weakens BF autoregulation.…”

“…35 Tested in rats, higher IOP is needed to attenuate ocular BF in animals with higher BP. 36 The results of these studies indicate a complicated interaction between BP and IOP on BF regulation.…”