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

BACKGROUND AND PURPOSE: 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.

EXPERIMENTAL APPROACH: 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.

KEY RESULTS: 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.

CONCLUSION AND IMPLICATIONS: α7-nAChR activation causes vasorelaxation of retinal capillaries.