HYPERCAPNIA IMPAIRS VASCULAR RESPONSES TO CHANGES IN OCULAR PERFUSION PRESSURE IN RAT RETINA

Abstract

Purpose : Retinal vascular resistance is constantly regulated by both myogenic and metabolic mechanisms. While most studies have investigated these mechanisms separately, how they interact to impact the vascular resistance is unclear. We considered whether hypercapnia (HC) modified the effect of ocular perfusion pressure (OPP) lowering, induced by lowering blood pressure (BP) or increasing intraocular pressure (IOP) on retinal vessel diameter (Ø).

Methods : In pentobarbital anesthetized Brown Norway rats, breathing ~30% O₂ air, normocapnia (NC) and hypercapnia (HC) were achieved by controlled ventilation. A gradual decrease in OPP, at the same rate for BP lowering or IOP elevation, was induced by drawing blood (1ml/min) from a femoral artery or by increasing the IOP manometrically from 10 to 70 mmHg (9.78 mmHg/min) in two subgroups for each NC (BP=7, IOP=9) and HC (BP=9, IOP=5). Arterial CO₂ partial pressure (pCO₂) was measured. In all groups, image sequences centered on the optic nerve were acquired with a confocal scanning laser ophthalmoscope (cSLO) every 1.5 minutes until OPP was < 20 mmHg. Arteries and veins at 1-disc diameter from optic nerve were analyzed. Change in Ø (%) was normalized to its own baseline (before pressure manipulation) and differences between NC and HC groups were compared.

Results : Average pCO₂levelwas 35 ±5 mmHg (n=12) in NC and 77 ±18 mmHg (n=10) in HC (p<0.001), and pO₂ was >80 mmHg for all animals. In the NC group, lowering BP induced progressive arterial and venous dilation (P<0.0001 and 0.005, respectively. Fig 1); increasing IOP caused vasodilatation in arteries (P<0.0001), but not in veins (P>0.05, Fig 2). Vasodilation was evident when OPP dropped to 50-60 mmHg for both BP and IOP modification. During HC, IOP and BP induced arterial vasodilation was significantly attenuated and venous diameter showed greater compression (P<0.0001 both, 2-way ANOVA) compared to the NC groups.

Conclusions : Carbon dioxide levels significantly modifies the capacity for retinal blood vessel to cope with reduction in OPP. This data show that the metabolic status of the retina profoundly impact vascular autoregulation, which has implication for metabolic diseases.

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