Abstract
Purpose: The present study aimed to investigate whether cervical vagal nerve stimulation (VNS) could prevent retinal ganglion cell (RGC) loss and retinal dysfunction after ischemia/reperfusion (I/R) injury.Methods: First, rats were randomly divided into sham group (n = 4) and VNS group (n = 12). Activation of the nodose ganglia (NOG), nucleus of the solitary tract (NTS), superior salivatory nucleus (SSN), and pterygopalatine ganglion (PPG) neural circuit were evaluated by c-fos expression at 0 h after sham VNS and at 0 h (n = 4), 6 h (n = 4), 72 h (n = 4) after VNS. Secondly, rats were randomly assigned to I/R group (pressure-induced retinal ischemia for 1 h and reperfusion for 1 h in the right eye, n = 16) and I/R+VNS group (right cervical VNS for 2 h during the I/R period, n = 16). The left eye of each rat served as a control. Electroretinogram (ERG), RGC numbers, tumor necrosis factor-α (TNF-α) and vasoactive intestinal polypeptide (VIP) levels in retina were determined. Additionally, the level of VIP in PPG was evaluated.Results: In the first part of the study, compared with the sham group, the VNS group exhibited significantly increased expression of c-fos in NOG, NTS, SSN, and PPG tissues at 0, 6, and 72 h. In the second part of the study, compared with left eyes, retinal function in right eyes (as assessed by the a-wave, b-wave and the oscillatory potential amplitudes of ERG and RGC data) was significantly decreased by I/R. The decreased retinal function was attenuated by VNS. In addition, I/R induced an increase in inflammation, which was reflected by elevated TNF-α expression in the retina. VNS significantly attenuated the increase in I/R-induced inflammation. Moreover, VIP expression in the retina and PPG, which may contribute to the inhibition of the inflammatory response, was significantly increased after VNS.Conclusion: VNS could protect against retinal I/R injury by downregulating TNF-α. Upregulation of VIP expression due to activation of the NOG-NTS-SSN-PPG neural circuit may underlie to the protective effects of VNS.
Highlights
Retinal ischemia/reperfusion (I/R) injury is a common pathological process that develops in a variety of retinal disorders including diabetic retinopathy, retinopathy of prematurity and glaucoma, resulting in the progressive loss of retinal ganglion cells (RGCs) and vision (Kaur et al, 2008; Narayanan et al, 2013; Palmhof et al, 2018)
vagal nerve stimulation (VNS) Increases C-Fos Expression in nodose ganglia (NOG)-nucleus of the solitary tract (NTS)-superior salivatory nucleus (SSN)-pterygopalatine ganglion (PPG) Neurons C-fos is a classical marker used to indicate the activation of neurons
To investigate neural pathway activation, the expressions of c-fos in the NTS, SSN, NOG, and PPG sections were analyzed by immunohistochemistry (n = 4/group)
Summary
Retinal ischemia/reperfusion (I/R) injury is a common pathological process that develops in a variety of retinal disorders including diabetic retinopathy, retinopathy of prematurity and glaucoma, resulting in the progressive loss of retinal ganglion cells (RGCs) and vision (Kaur et al, 2008; Narayanan et al, 2013; Palmhof et al, 2018). Acute elevation of intraocular pressure (IOP) followed by reperfusion was a well-established model used to investigate the mechanisms of, and potential therapy for retinal ischemia (Zheng et al, 2007; Mi et al, 2012; Palmhof et al, 2018). Chi et al (2014) used an acute IOP model to investigate the underlying mechanism of RGC death and found that IOP increases IL-1β expression and RGC death. Previous studies have shown that some medicines or operation can remit retinal reperfusion (I/R) injury (Adams et al, 2018; Le et al, 2018), the side effects and shortcomings of present therapy highlights the need for improved therapies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
