Relaxin 2 Is Functional at the Ocular Surface and Promotes Corneal Wound Healing

2012 ◽  
Vol 53 (12) ◽  
pp. 7780 ◽  
Author(s):  
Ulrike Hampel ◽  
Thomas Klonisch ◽  
Eugenia Makrantonaki ◽  
Saadettin Sel ◽  
Ute Schulze ◽  
...  
2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Martin Schicht ◽  
Fabian Garreis ◽  
Nadine Hartjen ◽  
Stephanie Beileke ◽  
Christina Jacobi ◽  
...  

Endocrinology ◽  
2013 ◽  
Vol 154 (6) ◽  
pp. 2034-2045 ◽  
Author(s):  
Ulrike Hampel ◽  
Thomas Klonisch ◽  
Saadettin Sel ◽  
Ute Schulze ◽  
Friedrich P. Paulsen

Abstract Tear fluid is known to contain many different hormones with relevance for ocular surface homeostasis. We studied the presence and functional role of insulin-like factor 3 (INSL3) and its cognate receptor RXFP2 (relaxin/insulin-like family peptide receptor 2) at the ocular surface and in tears. Expression of human INSL3 and RXFP2 was determined in tissues of the ocular surface and lacrimal apparatus; in human corneal (HCE), conjunctival (HCjE), and sebaceous (SC) epithelial cell lines; and in human tears by RT-PCR and ELISA. We investigated effects of human recombinant INSL3 (hrINSL3) on cell proliferation and cell migration and the influence of hrINSL3 on the expression of MMP2, -9, and -13 and TIMP1 and -2 was quantified by real-time PCR and ELISA in HCE, HCjE, and SC cells. We used a C57BL/6 mouse corneal defect model to elucidate the effect of topical application of hrINSL3 on corneal wound healing. INSL3 and RXFP2 transcripts and INSL3 protein were detected in all tissues and cell lines investigated. Significantly higher concentrations of INSL3 were detected in tears from male vs. female volunteers. Stimulation of HCE, HCjE, and SC with hrINSL3 significantly increased cell proliferation in HCjE and SC and migration of HCjE. Treatment with hrINSL3 for 24 hours regulated MMP2, TIMP1, and TIMP2 expression. The local application of hrINSL3 onto denuded corneal surface resulted in significantly accelerated corneal wound healing in mice. These findings suggest a novel and gender-specific role for INSL3 and cognate receptor RXFP2 signaling in ocular surface homeostasis and determined a novel role for hrINSL3 in corneal wound healing.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xingyue Yuan ◽  
Xiubin Ma ◽  
Lingling Yang ◽  
Qingjun Zhou ◽  
Ya Li

Abstract Background Topical application of β-blocker eye drops induces damage to the ocular surface in clinical. However, the mechanism involved remains incompletely understood. The purpose of this study was to investigate the influence and mechanism of β-blocker eye drops on corneal epithelial wound healing. Methods Corneal epithelial wound healing models were constructed by epithelial scraping including in the limbal region and unceasingly received eye drops containing 5 mg/mL β-blocker levobunolol, β1-adrenoceptor (β1AR)-specific antagonist atenolol or β2-adrenoceptor (β2AR)-specific antagonist ICI 118, 551. For the migration assay, the murine corneal epithelial stem/progenitor cells (TKE2) were wounded and subsequently incubated with levobunolol, atenolol, or ICI 118, 551. The proliferation and colony formation abilities of TKE2 cells treated with levobunolol, atenolol, or ICI 118, 551 were investigated by CCK-8 kit and crystal violet staining. The differentiation marker Cytokeratin 3 (CK3), the stem cell markers-Cytokeratin 14 (CK14) and Cytokeratin 19 (CK19), and corneal epithelium regeneration-related signaling including in Ki67 and the phosphorylated epithelial growth factor receptor (pEGFR) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) were assessed by immunofluorescence staining. Results Levobunolol and ICI 118, 551 impaired corneal wound healing, decreased the expressions of CK3, CK14, and CK19 after limbal region scraping in vivo and reduced the migration and proliferation of TKE2 in vitro, whereas atenolol had no significant effect. Moreover, levobunolol and ICI 118, 551 inhibited corneal wound healing by mediating the expression of Ki67, and the phosphorylation of EGFR and ERK1/2 in the limbal and regenerated corneal epithelium. Conclusion β-blocker eye drops impaired corneal wound healing by inhibiting the β2AR of limbal stem cells, which decreased corneal epithelial regeneration-related signaling. Therefore, a selective β1AR antagonist might be a good choice for glaucoma treatment to avoid ocular surface damage.


1963 ◽  
Vol 56 (5) ◽  
pp. 833-834
Author(s):  
N.A. Wine ◽  
P.K. Basu

2011 ◽  
Vol 52 (9) ◽  
pp. 6213 ◽  
Author(s):  
Andri K. Riau ◽  
Romesh I. Angunawela ◽  
Shyam S. Chaurasia ◽  
Wing S. Lee ◽  
Donald T. Tan ◽  
...  

2018 ◽  
Vol 192 ◽  
pp. 240-250 ◽  
Author(s):  
Wenhua Xu ◽  
Zheying Wang ◽  
Ying Liu ◽  
Liping Wang ◽  
Zhiwen Jiang ◽  
...  

1969 ◽  
Vol 53 (6) ◽  
pp. 407-411 ◽  
Author(s):  
G B Hubbard ◽  
B E Herron ◽  
J S Andrews ◽  
J H Elliott

Sign in / Sign up

Export Citation Format

Share Document