Neprilysin inhibition promotes corneal wound healing

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.

Neprilysin expression and functions in development, ageing and disease

“…NEP inhibition was also suggested for treatment of corneal injury and corneal wound healing ( Genova et al, 2018 ). Another proposed area for NEP inhibitor application was female sexual arousal disorders although no significant progress in this area has been achieved ( Angulo, 2010 ).…”

Targeting amyloid clearance in Alzheimer's disease as a therapeutic strategy

“…The dual cardioprotective action of the drug appears to have significant advantages in the management of heart failure (the PARADIGM‐HF Phase III trial; McMurray et al, ). NEP inhibition may also provide novel therapeutic benefits in corneal injury by promoting corneal wound healing (Genova, Meyer, Anderson, Harper, & Pieper, ). However, long‐term side effects of chronic NEP inhibition, such as a potential for promoting amyloid accumulation in the brain, and consequent dementia, as well as angioedema because of other physiological substrates of NEP, particularly bradykinin, still remain to be fully assessed (Campbell, ).…”

Ovalbumin’s potential as a wound-healing medicament in tooth extraction socket by induction of cell proliferation through the ERK2 pathway in silico

“…28 Meanwhile, the inhibition of corneal MME is known to improve corneal epithelial wound healing in mice. 29 Eliminating CASP8 is known to increase the proliferation and migration of human epidermal keratinocytes, which can promote wound healing in mice. 30 Molecular docking analysis results show that peptide fragments VY (F6), AAH (F1), GSIGAASM (F3) and require the lowest binding energy.…”