Retinal Autoregulation: Flow–Induced Response in Retinal Arterioles

Abstract

Abstract: : Purpose: Autoregulation has been demonstrated in the retinal vasculature in various animal models and in humans; however, the underlying mechanisms contributing to the control of retinal blood flow are not known. Changes in local hemodynamics (i.e., pressure and flow) may contribute significantly to retinal arteriolar blood flow regulation. To determine whether retinal arterioles respond to changes in blood flow, we characterized the flow–induced response in isolated retinal arterioles without confounding influences from systemic or local neural, humoral, hemodynamic, and metabolic changes. Methods: Two different sizes of retinal arterioles (120–200 µm and 80–120 µm corresponding to first– and second–order arterioles, respectively) were isolated from the porcine retina, cannulated, and pressurized in a dual–reservoir system. After an equilibration period, the flow–diameter relation was determined by measuring the internal diameter with a videomicrometer after the initiation of flow by simultaneously moving the two reservoirs in equal and opposite directions, which generates a pressure gradient between the two reservoirs. The vessel diameter was measured at each level of flow corresponding to a pressure gradient of 2, 4, 10, 20, 40, and 60 cmH₂O. The vessel diameter stabilized within 5 minutes after a change in flow. At the end of each experiment, the flow was returned to zero and the vessels were dilated with nitroprusside (10^–4 M) in calcium free PSS to obtain the maximal diameter. Results: First– and second–order arterioles achieved 70% maximal dilation at a similar pressure gradient for flow (40 cmH₂O); however, second–order arterioles exhibited greater sensitivity to changes in flow at lower pressure gradients for flow (2–20 cmH₂O). The greatest difference in the flow–induced response between first– and second–order arterioles occurred at a pressure gradient for flow of 10 cmH₂O (i.e., 20% maximal dilation in first–order arterioles compared to 60% maximal dilation in second–order arterioles). Conclusions: This in vitro study demonstrates a flow–induced response in isolated porcine retinal arterioles and the differences in this response between first– and second–order arterioles. These findings suggest that the retinal microvascular network exhibits heterogeneous flow–induced responses and that these flow–induced responses actively contribute to the autoregulation of retinal blood flow.

Keywords: neuroprotection • retina • nitric oxide