PMID- 35427568 OWN - NLM STAT- MEDLINE DCOM- 20220526 LR - 20230916 IS - 1096-0007 (Electronic) IS - 0014-4835 (Print) IS - 0014-4835 (Linking) VI - 219 DP - 2022 Jun TI - Expression of axon guidance ligands and their receptors in the cornea and trigeminal ganglia and their recovery after corneal epithelium injury. PG - 109054 LID - S0014-4835(22)00134-8 [pii] LID - 10.1016/j.exer.2022.109054 [doi] AB - Axon guidance proteins are essential for axonal pathfinding during development. In adulthood, they have been described as pleiotropic proteins with multiple roles in different organs and tissues. While most studies on the roles of these proteins in the cornea have been performed on the Semaphorin family members, with few reports on Netrins or Ephrins, their function in corneal epithelium wound healing and functional nerve regeneration is largely unknown. Here, we studied the expression of ligands belonging to three distinct axon guidance families (Semaphorins, Ephrins, and Netrins) and their most commonly associated receptors in the cornea and trigeminal ganglia (TG) using immunofluorescence staining and RT-qPCR. We also evaluated how their expression recovers after corneal epithelium injury. We found that all ligands studied (Sema3A, Sema3F, EphrinB1, EphrinB2, Netrin-1, and Netrin-4) are abundantly expressed in both the TG and corneal epithelium. Similarly, their receptors (Neuropilin-1, Neuropilin-2, PlexinA1, PlexinA3, EphB2, EphB4, Neogenin, UNC5H1 and DCC) are also expressed in both tissues. Upon corneal epithelium injury, quick recovery of both ligands and receptors was observed at the protein and gene expression levels. While the timing and expression levels vary among these proteins, in general, most of them remained upregulated for several weeks after injury. We propose that the initial protein expression recovery may be related to corneal epithelium recovery since Sema3A, EphrinB2 and Netrin-4 accelerated corneal epithelial cells wound healing. The sustained high expression levels may be functionally related to nerve regeneration and/or patterning. Whilst further studies are required to test this hypothesis, this work contributes to unraveling their function in normal and injured cornea. CI - Copyright (c) 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Guaiquil, Victor H AU - Guaiquil VH AD - Department of Ophthalmology and Visual Sciences, University of Illinois-Chicago, Chicago, IL, USA. Electronic address: vguaiqui@uic.edu. FAU - Xiao, Cissy AU - Xiao C AD - Department of Ophthalmology and Visual Sciences, University of Illinois-Chicago, Chicago, IL, USA. FAU - Lara, Daniel AU - Lara D AD - Department of Ophthalmology and Visual Sciences, University of Illinois-Chicago, Chicago, IL, USA. FAU - Dimailig, Greigory AU - Dimailig G AD - Department of Ophthalmology and Visual Sciences, University of Illinois-Chicago, Chicago, IL, USA. FAU - Zhou, Qiang AU - Zhou Q AD - Department of Ophthalmology and Visual Sciences, University of Illinois-Chicago, Chicago, IL, USA. LA - eng GR - P30 EY001792/EY/NEI NIH HHS/United States GR - R01 EY027912/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20220412 PL - England TA - Exp Eye Res JT - Experimental eye research JID - 0370707 RN - 0 (Ephrins) RN - 0 (Ligands) RN - 0 (Membrane Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Netrins) RN - 0 (SEMA3F protein, human) RN - 0 (Semaphorin-3A) SB - IM MH - Adult MH - Axon Guidance MH - Cornea/metabolism MH - Ephrins/metabolism MH - *Epithelium, Corneal/metabolism MH - Humans MH - Ligands MH - Membrane Proteins/metabolism MH - Nerve Tissue Proteins/metabolism MH - Netrins/metabolism MH - Semaphorin-3A/genetics/metabolism MH - Trigeminal Ganglion/metabolism PMC - PMC9133167 MID - NIHMS1800321 OTO - NOTNLM OT - Axon guidance proteins OT - Cornea wound healing OT - Ephrin OT - Netrin OT - Semaphorin EDAT- 2022/04/16 06:00 MHDA- 2022/05/27 06:00 PMCR- 2022/06/01 CRDT- 2022/04/15 20:10 PHST- 2021/11/07 00:00 [received] PHST- 2022/03/15 00:00 [revised] PHST- 2022/03/22 00:00 [accepted] PHST- 2022/04/16 06:00 [pubmed] PHST- 2022/05/27 06:00 [medline] PHST- 2022/04/15 20:10 [entrez] PHST- 2022/06/01 00:00 [pmc-release] AID - S0014-4835(22)00134-8 [pii] AID - 10.1016/j.exer.2022.109054 [doi] PST - ppublish SO - Exp Eye Res. 2022 Jun;219:109054. doi: 10.1016/j.exer.2022.109054. Epub 2022 Apr 12.