The role of neprilysin in ocular surface homeostasis and corneal wound healing

The cornea is a transparent, dome-shaped structure that focuses incoming light and provides a physical barrier against infection and damage to the eye. As the outermost tissue of the eye, the cornea is vulnerable to injury, an underreported and globally significant cause of vision loss. While superficial wounds are easily and rapidly repaired, extensive injury can overwhelm the ability of the cornea to heal normally. This can result in scarring, ulceration, and ultimately, compromised visual acuity. Depending on the extent of injury, both medical and surgical interventions may be required to restore corneal transparency. However, visual prognosis after severe corneal injury often remains guarded, even with our current treatment strategies. Increasing our understanding of corneal wound healing mechanisms is therefore critical for development of improved therapies for corneal injury.

The work in this dissertation employs a mouse model of corneal injury to investigate wound healing mechanisms that we hypothesize could be targeted to accelerate recovery and improve outcomes in human patients. We focus on the role of neprilysin (NEP), an enzyme involved in modulating inflammation throughout the body. Using genetic and pharmacologic approaches, we characterize the contribution of NEP to maintenance of the uninjured cornea and to repair of the chemically injured cornea. Overall, we provide insight into corneal wound healing mechanisms and identify NEP as a potential therapeutic target for treating severe corneal injury.