Sympathetic activation leads to Schlemm's canal expansion via increasing vasoactive intestinal polypeptide secretion from trabecular meshwork

Dingwen Xu; Feipeng Wu; Yixian Yu; Xiaotong Lou; Meng Ye; Hong Zhang; Yin Zhao

doi:10.1016/j.exer.2022.109235

Sympathetic activation leads to Schlemm's canal expansion via increasing vasoactive intestinal polypeptide secretion from trabecular meshwork

Exp Eye Res. 2022 Nov:224:109235. doi: 10.1016/j.exer.2022.109235. Epub 2022 Aug 30.

Authors

Dingwen Xu¹, Feipeng Wu¹, Yixian Yu¹, Xiaotong Lou¹, Meng Ye¹, Hong Zhang², Yin Zhao³

Affiliations

¹ Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
² Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: tjyksys@163.com.
³ Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: zhaoyin85@hust.edu.cn.

PMID: 36049555
DOI: 10.1016/j.exer.2022.109235

Abstract

We previously demonstrated vasoactive intestinal polypeptide (VIP) eyedrops reduce intraocular pressure (IOP) and stabilize cytoskeleton of the Schlemm's canal (SC) endothelium in a chronic ocular hypertension rat model. Here we determine if the trabecular meshwork (TM) releases endogenous VIP and affect SC in paracrine manner, and whether this cellular interaction via VIP is strengthened under stimulated sympathetic activity. A rat model of moderate-intensity exercise was established to stimulate sympathetic activation. IOP post exercise was measured by a rebound tonometer. Sympathetic nerve activity at the TM was immunofluorescence-stained with DβH and PGP9.5. Morphological changes of TM and SC were quantitatively measured by hematoxylin-eosin (HE) staining. Further, epinephrine was applied to mimic sympathetic excitation on primary rat TM cells, and ELISA to measure VIP levels in the medium. The cytoskeleton protective effect of VIP in the epinephrine-stimulated conditioned medium (Epi-CM) was evaluated in oxidative stressed human umbilical vein endothelial cells (HUVECs). Elevated sympathetic nerve activity was found at TM post exercise. Changes accompanying the sympathetic excitation included thinned TM, expanded SC and decreased IOP, which were consistent with epinephrine treatment. Epinephrine decreased TM cell size, enhanced VIP expression and release in the medium in vitro. Epi-CM restored linear F-actin and cell junction integrity in H₂O₂ treated HUVECs. Blockage of VIP receptor by PG99-465 attenuated the protective capability of Epi-CM. VIP expression was upregulated at TM and the inner wall of SC post exercise in vivo. PG99-465 significantly attenuated exercise-induced SC expansion and IOP reduction. Thus, the sympathetic activation promoted VIP release from TM cells and subsequently expanded SC via stabilizing cytoskeleton, which resulted in IOP reduction.

Keywords: Epinephrine; Exercise; Schlemm's canal; Sympathetic activation; Trabecular meshwork; Vasoactive intestinal polypeptide.

Publication types

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

MeSH terms

Actins / metabolism
Animals
Culture Media, Conditioned / pharmacology
Epinephrine / metabolism
Human Umbilical Vein Endothelial Cells
Humans
Hydrogen Peroxide / pharmacology
Intraocular Pressure
Ophthalmic Solutions / pharmacology
Rats
Receptors, Vasoactive Intestinal Peptide / metabolism
Trabecular Meshwork* / metabolism
Vasoactive Intestinal Peptide* / metabolism
Vasoactive Intestinal Peptide* / pharmacology

Substances

Actins
Culture Media, Conditioned
Epinephrine
Hydrogen Peroxide
Ophthalmic Solutions
Receptors, Vasoactive Intestinal Peptide
Vasoactive Intestinal Peptide