scholarly journals Serp-1 change globally Promotes Corneal Wound Healing by Facilitating Re-epithelialization and Inhibiting Fibrosis and Angiogenesis

2021 ◽  
Vol 8 ◽  
Author(s):  
Brent Ju ◽  
Owen Guo ◽  
Dathe Z. Benissan-Messan ◽  
McKinley H. Shawver ◽  
Peng Chen ◽  
...  

Purpose: Chemical corneal injuries carry a high morbidity and commonly lead to visual impairment. Here, we investigate the role of Serp-1, a serine protease inhibitor, in corneal wound healing.Methods: An alkaline-induced corneal injury was induced in 14 mice. Following injury, five mice received daily topical saline application while nine mice received Serp-1 100 μL topically combined with a daily subcutaneous injection of 100 ng/gram body weight of Serp-1. Corneal damage was monitored daily through fluorescein staining and imaging. Cross sectional corneal H&E staining were obtained. CD31 was used as marker for neovascularization.Results: Serp-1 facilitates corneal wound healing by reducing fibrosis and neovascularization while mitigating inflammatory cell infiltration with no noticeable harm related to its application.Conclusions: Serp-1 effectively mitigates inflammation, decreases fibrosis, and reduce neovascularization in a murine model of corneal injury without affecting other organs.Translational Relavence: Our study provides preclinical data for topical application of Serp-1 to treat corneal wounds.

2019 ◽  
Vol 182 ◽  
pp. 74-84 ◽  
Author(s):  
Natalia Murataeva ◽  
Sally Miller ◽  
Amey Dhopeshwarkar ◽  
Emma Leishman ◽  
Laura Daily ◽  
...  

PLoS ONE ◽  
2011 ◽  
Vol 6 (6) ◽  
pp. e21180 ◽  
Author(s):  
Giuseppina Marrazzo ◽  
Lars Bellner ◽  
Adna Halilovic ◽  
Giovanni Li Volti ◽  
Filippo Drago ◽  
...  

2015 ◽  
Vol 56 (6) ◽  
pp. 3673 ◽  
Author(s):  
Jianhong An ◽  
Xiaoyan Chen ◽  
Weiwei Chen ◽  
Rongxin Liang ◽  
Peter S. Reinach ◽  
...  

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Kyu-Yeon Han ◽  
Jennifer A. Tran ◽  
Jin-Hong Chang ◽  
Dimitri T. Azar ◽  
James D. Zieske

Cornea ◽  
2013 ◽  
Vol 32 ◽  
pp. S43-S45 ◽  
Author(s):  
Osamu Yamanaka ◽  
Takayoshi Sumioka ◽  
Shizuya Saika

2020 ◽  
Author(s):  
Ada Admin ◽  
Yangyang Zhang ◽  
Nan Gao ◽  
Lin Wu ◽  
Patrick S. Y. Lee ◽  
...  

Diabetic Keratopathy, a sight-threatening corneal disease, comprises several symptomatic conditions including delayed epithelial wound healing, recurrent erosions, and sensory nerve (SN) neuropathy. We investigated the role of neuropeptides in mediating corneal wound healing, including epithelial wound closure and SN regeneration. Denervation by Resiniferatoxin severely impaired corneal wound healing and markedly up-regulated pro-inflammatory gene expression. Exogenous neuropeptides CGRP, SP, and VIP partially reversed Resiniferatoxin’s effects, with VIP specifically inducing IL-10 expression. Hence, we focused on VIP and observed that wounding induced VIP and VIPR1 expression in normal (NL), but not diabetic (DM) mouse corneas. Targeting VIPR1 in <em>NL</em> corneas attenuated corneal wound healing, dampened wound-induced expression of neurotrophic factors, and exacerbated inflammatory responses while exogenous VIP had the opposite effects in DM corneas. Remarkably, wounding and diabetes also affected the expression of Sonic Hedgehog (SHH) in a VIP-dependent manner. Downregulating SHH expression in NL corneas decreased, while exogenous SHH in DM corneas increased the rates of corneal wound healing. Furthermore, inhibition of SHH signaling dampened VIP-promoted corneal wound healing. We conclude that VIP regulates epithelial wound he<a></a><a>aling, inflammatory response, and nerve regeneration in the corneas in a</a> SHH-dependent manner, suggesting a therapeutic potential for these molecules in treating diabetic keratopathy.


2018 ◽  
Vol 166 ◽  
pp. 49-55 ◽  
Author(s):  
Hidetaka Miyagi ◽  
Sara M. Thomasy ◽  
Paul Russell ◽  
Christopher J. Murphy

2002 ◽  
Vol 283 (6) ◽  
pp. C1646-C1654 ◽  
Author(s):  
De-An Wang ◽  
Haiming Du ◽  
Jonathan H. Jaggar ◽  
David N. Brindley ◽  
Gabor J. Tigyi ◽  
...  

The phospholipid growth factors (PLGFs), including lysophosphatidic acid (LPA), have been implicated in corneal wound healing. PLGF concentrations and activities are elevated after corneal injury. Using real-time PCR, we quantified receptor mRNA levels in the healing rabbit cornea. In intact corneas, transcripts for S1P1, LPA1, and LPA3 receptor subtypes were detected, as was lipid phosphate phosphatase 1 (LPP1). After wounding, the trend for endothelium and keratocytes was for significant decreases in transcript numbers for the three receptor subtypes, whereas epithelial cells showed increased transcript numbers, except for an S1P1 decrease in healing cells. LPP1 transcript numbers were decreased in keratocytes and endothelium, although LPP-specific activity was unchanged. LPA-elicited Ca2+ transients were significantly reduced in the healing endothelium. Consistent with reduced LPA3 receptor numbers, dioctylglycerol pyrophosphate, a selective antagonist, reduced LPA-induced Ca2+ transients 2.7-fold in nonwounded epithelium but only 1.5-fold in wound-healing endothelium. These data for the first time establish physiologically relevant differential changes in the expression of PLGF receptor subtypes and provide evidence for the changing role of LPA3 receptors in endothelial cells.


2004 ◽  
Vol 78 (3) ◽  
pp. 579-589 ◽  
Author(s):  
Eric Gabison ◽  
Jin-Hong Chang ◽  
Everardo Hernández-Quintela ◽  
Joel Javier ◽  
Paul C.S. Lu ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document