Alpha 7-nicotinic cholinoceptor regulation of pericyte-containing retinal capillaries

Kaicheng Wu; Tongjie Cheng; Zimeng Zhai; Chunhui Jiang; Xujiao Zhou

doi:10.1111/bph.16067

Alpha 7-nicotinic cholinoceptor regulation of pericyte-containing retinal capillaries

Br J Pharmacol. 2023 Sep;180(17):2196-2213. doi: 10.1111/bph.16067. Epub 2023 Apr 23.

Authors

Kaicheng Wu^{1

2

3

4}, Tongjie Cheng^{1

2

3

4}, Zimeng Zhai^{1

2

3

4}, Chunhui Jiang^{1

2

3

4}, Xujiao Zhou^{1

2

3

4}

Affiliations

¹ Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, Shanghai, 200032, China.
² Eye Institute, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
³ Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200032, China.
⁴ NHC Key Laboratory of Myopia, Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Fudan University, Shanghai, 200032, China.

PMID: 36908011
DOI: 10.1111/bph.16067

Abstract

Background and purpose: Local blood flow regulation relies on the coordination between neurons and pericyte-containing capillaries. Pericyte relaxation and contraction are influenced by vasoactive substances and regulated by neurotransmitters. α7 nicotinic acetylcholine receptors (α7-nAChRs), involved in the regulation of vascular function and inhibitory γ-aminobutyric acid (GABA) systems, have neuroprotective effects against CNS diseases. Although α7-nAChRs are found throughout the retina, their contribution to the retinal capillary tone remains unknown. Here, we investigated the neurovascular coupling mechanism underlying α7-nAChR-mediated retinal capillary tone regulation.

Experimental approach: Changes in capillary diameter and pericyte transverse diameter during drug perfusion were observed using differential interference contrast (DIC) microscopy, to help elucidate signalling pathways underlying α7-nAChR-mediated regulation of capillary blood flow at the whole retinal level. Patch clamp technique was used to investigate α7-nAChR-mediated regulation of the 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 endothelial nitric oxide synthase (eNOS), resulting in dilated retinal capillaries and pericytes via the nitric oxide synthase (NOS)/nitric oxide (NO)/guanosine 3',5'- monophosphate (cGMP) signalling pathway. Neuronal α7-nAChR activation directly relaxed retinal capillaries and pericytes via a neurovascular coupling mechanism. α7-nAChR also increased the vesicular release of GABA, possibly promoting the release of NO by binding to GABA_A receptors in retinal ganglion cells (RGCs) and relaxing blood vessels via eNOS-NO, with GABA binding to GABA_B receptors on retinal capillary endothelial cells.

Conclusion and implications: α7-nAChR activation causes vasorelaxation of retinal capillaries.

Keywords: GABA; pericyte; retinal capillaries; signalling pathway; α7 nicotinic acetylcholine receptor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Capillaries / metabolism
Endothelial Cells / metabolism
Pericytes* / metabolism
Receptors, Nicotinic* / metabolism
Retina / metabolism
gamma-Aminobutyric Acid / metabolism

Substances

Receptors, Nicotinic
gamma-Aminobutyric Acid