Neprilysin inhibition promotes corneal wound healing

Rachel M Genova; Kacie J Meyer; Michael G Anderson; Matthew M Harper; Andrew A Pieper

doi:10.1038/s41598-018-32773-9

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Neprilysin inhibition promotes corneal wound healing

Journal article

Open access

Peer reviewed

Neprilysin inhibition promotes corneal wound healing

Rachel M Genova, Kacie J Meyer, Michael G Anderson, Matthew M Harper and Andrew A Pieper

Scientific reports, Vol.8(1), pp.14385-11

09/26/2018

DOI: 10.1038/s41598-018-32773-9

PMCID: PMC6158251

PMID: 30258206

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https://doi.org/10.1038/s41598-018-32773-9View

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Abstract

Neprilysin (NEP), an ectoenzyme that modulates inflammation by degrading neuropeptides, was recently identified in the human corneal epithelium. The cornea expresses many NEP substrates, but the function of NEP in homeostatic maintenance and wound healing of the cornea is unknown. We therefore investigated the role of this enzyme under naive and injured conditions using NEP-deficient (NEP ) and wild type (WT) control mice. In vivo ocular surface imaging and histological analysis of corneal tissue showed no differences in limbal vasculature or corneal anatomy between naive NEP and WT mice. Histological examination revealed increased corneal innervation in NEP mice. In an alkali burn model of corneal injury, corneal wound healing was significantly accelerated in NEP mice compared to WT controls 3 days after injury. Daily intraperitoneal administration of the NEP inhibitor thiorphan also accelerated corneal wound healing after alkali injury in WT mice. Collectively, our data identify a previously unknown role of NEP in the cornea, in which pharmacologic inhibition of its activity may provide a novel therapeutic option for patients with corneal injury.

Details

Title: Subtitle: Neprilysin inhibition promotes corneal wound healing
Creators: Rachel M Genova - Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Kacie J Meyer - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Michael G Anderson - Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Matthew M Harper - Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, IA, USA. matthew-harper@uiowa.edu
Andrew A Pieper - Harrington Discovery Institute, University Hospital Case Medical Center, Department of Psychiatry, Case Western Reserve University, Geriatric Research Education and Clinical Centers, Louis Stokes Cleveland VAMC, Cleveland, OH, USA. AndrewAPieper@gmail.com
Resource Type: Journal article
Publication Details: Scientific reports, Vol.8(1), pp.14385-11
DOI: 10.1038/s41598-018-32773-9
PMID: 30258206
PMCID: PMC6158251
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Grant note: I01 RX001481 / RRD VA P30 EY025580 / NEI NIH HHS T32 GM007337 / NIGMS NIH HHS R01 EY017673 / NEI NIH HHS
Language: English
Date published: 09/26/2018
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Biology; Ophthalmology and Visual Sciences
Record Identifier: 9984172168602771

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