Alpha 7-nicotinic cholinergic regulation of pericyte-containing retinal capillaries.

Abstract

Local blood flow regulation relies mostly on the coordination between neurons and pericyte-containing capillaries. Pericyte relaxation and contraction are influenced by various vasoactive substances and regulated by neurotransmitters. α7 nicotinic acetylcholine receptors (α7-nAChRs), involved in the regulation of vascular function and inhibitory GABA systems, have neuroprotective effects against central nervous system diseases. Although α7-nAChRs are found throughout the retina, their contribution to the retinal capillary tone remains unknown. Here we investigate the neurovascular coupling mechanism underlying α7-nAChR-mediated retinal capillary tone regulation. Changes in capillary diameter and transverse diameter of pericytes during drug perfusion were observed using differential interference contrast microscopy (DIC) to elucidate signaling pathways underlying α7-nAChR-mediated regulation of capillary blood flow at the whole retinal level. Patch clamp technique was used to investigate α7-nAChRs-mediated regulation of the γ-aminobutyric acid (GABA) synaptic circuit. Immunofluorescence was used to explore the expression of α7-nAChRs and GABA receptors. Activating α7-nAChRs on the endothelial cell membrane caused perinuclear accumulation of eNOS. This resulted in dilated retinal capillaries and pericytes via the NOS/NO-cGMP signaling pathway. Neuronal α7-nAChRs activation relaxed retinal capillaries and pericytes via a neurovascular coupling mechanism. α7-nAChR increased the vesicular release of GABA, possibly promoting the release of NO by binding to GABAA receptors in retinal ganglionic cells (RGCs), and relaxation of blood vessels via eNOS-NO by binding to GABAB receptors on retinal capillary endothelial cells. α7-nAChR activation causes vasorelaxation of retinal capillaries.