HETEROGENEOUS EFFECTS OF GLIA ON BP- AND IOP-INDUCED RETINAL VASCULAR RESPONSES

Abstract

Purpose : We considered whether glial cell contribute to the capacity of the retinal vasculature to cope (vascular autoregulation) with changes in ocular perfusion pressure (OPP) induced by either IOP or blood pressure (BP).

Methods : Pentobarbital anesthetized Brown Norway rats were mechanically ventilated with 30% O₂ air. OPP was slowly reduced by either drawing blood from a femoral artery (1ml/min) or by manometrically increasing IOP from 10 to 70 mmHg at a similar rate (-0.16±0.4mmHg/s) (n=7 & 9, respectively). Prior to and during OPP reduction, confocal scanning laser ophthalmoscopy was used to acquire optic nerve centered images. Vessels at 1-disc diameter from the optic nerve margin were assess for OPP induced changes in vessel diameter (% relative to baselines). In two treatment groups (n=7 each), L-2-aminoadipic acid (LAA, 10 nM) was intravitreally injected to inhibit retinal glial activity 24-h prior to experiments. Responses between eyes with and without LAA treatment were compared.

Results : Throughout experiments, arterial CO₂ and O₂ partial pressures were maintained within 30-40 mmHg and >80 mmHg, respectively. In control eyes (Fig 1 & 2, red), BP lowering caused significant arterial and venous dilation (all P<0.01, 2-way ANOVA) starting at OPP 50±1 and 64 ±2mmHg (segmental linear regression), respectively. IOP elevation induced arterial dilation (P<0.01) starting at OPP 30±2mmHg, but caused no venous change (P>0.05). In eyes pretreated with LAA (Fig 1 & 2, blue), there was significantly less arterial and venous dilation in response to BP lowering, and less venous dilation during IOP elevation (all P<0.001, 2-way ANOVA) compared with control eyes.

Conclusions : BP- and IOP-induced OPP reduction produced similar arterial dilation, however, veins showed less dilation with IOP elevation compared with BP lowering. Inhibition of glial activity significantly blunted BP-induced arterial and venous responses, whereas glial inhibition impacted venous responses to IOP-elevation but not the arterial response. Glial activity contributes to the regulation of both arteries and veins, although this effect appears to be greater in veins.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.