Sympathetic activation leads to Schlemm's canal expansion via increasing vasoactive intestinal polypeptide secretion from trabecular meshwork. (November 2022)

• Record Type: Journal Article
• Authors: Xu, Dingwen; Wu, Feipeng; Yu, Yixian; Lou, Xiaotong; Ye, Meng; Zhang, Hong; Zhao, Yin
• Is Part Of: Experimental eye research. Volume 224(2022)
• Publication Date: 2022-11
• Subjects: Vasoactive intestinal polypeptide -- Trabecular meshwork -- Schlemm's canal -- Epinephrine -- Sympathetic activation -- Exercise; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2022.109235
• Languages: English
• ISSNs: 0014-4835

Abstract

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 H2 O2 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. Highlights: Sympathetic activation leads to increased VIP expression and secretion from TM cells. The conditioned medium derived from TM cells stabilizes HUVECs cytoskeleton via paracrine VIP. Exercise induced reduction of IOP was partly attenuated by VIP receptor antagonist. Promoting cellular interaction between TM and SC via VIP might be an option for IOP maintenance.