2. Academic Validation
  3. R-(+)-WIN55212-2 protects pericytes from ischemic damage and restores retinal microcirculatory patency after ischemia/reperfusion injury

R-(+)-WIN55212-2 protects pericytes from ischemic damage and restores retinal microcirculatory patency after ischemia/reperfusion injury

  • Biomed Pharmacother. 2023 Aug 10;166:115197. doi: 10.1016/j.biopha.2023.115197.
Jiaojiao Wei 1,  Lili Zhang 1,  Kaicheng Wu 1,  Jian Yu 1,  Fengjuan Gao 1,  Jingyi Cheng 1,  Ting Zhang 1,  Xujiao Zhou 2,  Yuan Zong 3,  Xiaojing Huang 4,  Chunhui Jiang 1
Affiliations

Affiliations

  • 1 Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, Shanghai 200031, People's Republic of China; Eye and ENT Hospital, State Key laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200031, People's Republic of China; Key Laboratory of Myopia of State Health Ministry, and Key Laboratory of Visual Impairment and Restoration of Shanghai, Shanghai 200031, People's Republic of China.
  • 2 Eye and ENT Hospital, State Key laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200031, People's Republic of China; Key Laboratory of Myopia of State Health Ministry, and Key Laboratory of Visual Impairment and Restoration of Shanghai, Shanghai 200031, People's Republic of China. Electronic address: xujiaozhou@126.com.
  • 3 Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, Shanghai 200031, People's Republic of China; Eye and ENT Hospital, State Key laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200031, People's Republic of China; Key Laboratory of Myopia of State Health Ministry, and Key Laboratory of Visual Impairment and Restoration of Shanghai, Shanghai 200031, People's Republic of China. Electronic address: zongyuan326@163.com.
  • 4 Department of Ophthalmology, Shanghai Pudong New Area Gongli Hospital, Shanghai 200135, People's Republic of China. Electronic address: 13917000235@163.com.
PMID: 37572634 DOI: 10.1016/j.biopha.2023.115197
Abstract

Background and purpose: Cannabinoids are vasoactive substances that act as key regulators of arterial tone in the blood vessels supplying peripheral tissues and the central nervous system. We investigated the effects of cannabinoids on retinal capillaries and pericytes.

Experimental approach: The effect of cannabinoids on capillary diameters was determined in an ex vivo whole-mount rat retinal model. Western blotting, quantitative PCR, and immunohistochemistry were performed to examine the underlying mechanism.

Key results: Endogenous cannabinoids 2-arachidonoylglycerol and anandamide and exogenous cannabinoid (R-(+)-WIN55212-2) dilated noradrenaline-precontracted capillaries in a concentration-dependent manner (1 μM to 0.1 mM). The extent of vasorelaxation correlated positively with changes in pericyte width. The effects of R-(+)-WIN55212-2 on vasorelaxation and pericyte width were inhibited by a Cannabinoid Receptor type 1 (CB1) antagonist.

Conclusions & implications: The exogenous cannabinoid R-(+)-WIN55212-2 promotes the vasorelaxation of pericyte-containing rat retinal capillaries. This effect of R-(+)-WIN55212-2 is dependent on CB1 and the nitric oxide-cyclic guanosine monophosphate pathway and requires an intact endothelium.

Keywords

Cannabinoid; Ischemia/reperfusion injury; Pericytes; Retinal microcirculatory.

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