Topical Hepatocyte Growth Factor for Corneal Regeneration and Reversal of Scarring
Abstract
Objectives and Rationale of Project: The cornea is the clear dome-shaped structure that comprises the very front of the eye; its clarity and proper shape are required for good vision. Because of its position, it is the most common site of ocular injury, infection, or other forms of inflammatory damage. Regardless of cause, the most frequent common denominator of vision loss from corneal injury or infection is scarring. Scarring occurs when overly exuberant normal healing processes of the body lead to replacement of normal tissue by fibrous connective tissue. When severe, scarring is associated with the tissue s loss of function, whether in the kidney, heart, lungs, skin, or the eye. In the eye, scarring induces not only opacity in the otherwise clear cornea, but also induces alterations in the shape and refractive power of the cornea (causing irregular astigmatism), which impact vision. According to the IRIS Registry of the American Academy of Ophthalmology, there are over 670,000 cases of corneal scarring diagnosed in the United States annually. Among the military alone, the ever-rising incidence of ocular injuries among warfighters has led to an incidence of 12% for corneal and scleral lacerations, underscoring the burden of potentially scar-inducing injuries among the deployed military personnel. How the Proposal Addresses an Area of High Unmet Need: Two facts highlight the area of high unmet need that we intend to address with our research. First, there is no good therapy for suppressing scarring. Corticosteroids are commonly used for this indication, but have myriad side-effects, including causing ocular hypertension/glaucoma, cataract development, and exacerbating infection, among others. Other agents used to suppress scarring, such as the chemotherapeutic agents mitomycin-C and 5-fluorouracil, are highly toxic, with serious complications such as ocular thinning and perforation. More important, all the available anti-scarring pharmaceutical agents in use delay wound healing, which itself is a major complication. Second, and perhaps more importantly, there is currently no treatment whatsoever for reversing scarring. This is an important distinction: While many anti-inflammatory and pro-regenerative approaches have been proposed for reducing the risk of new scarring, none have been developed to restore transparency to the previously scarred cornea. Indeed, today, the only definitive therapy for restoring clarity to the scarred cornea is transplantation, with its attendant risks and limitations: (1) access to specialized equipment, supplies, and subspecialty care, which are often not immediately available; (2) corneal sutures often induce optical irregularities that impede vision; (3) corneal grafting requires eye bank tissue; (4) there is the perpetual risk of immune rejection; and (5) high costs. The Science Behind Hepatocyte Growth Factor (HGF): HGF is unique in its biologic ability to concurrently potently (i) suppress scarring, (ii) promote wound healing, (iii) induce immune quiescence, and (iv) reverse scarring by inducing tissue remodeling. Our published work has already established the strong ability of HGF to promote closure of epithelial wounds while suppressing scarring and inflammation through well-defined mechanisms. What we are excited to pursue now is our preliminary data, detailed in the grant application, that show the remarkable capacity of HGF to reverse already formed scars in the cornea in response to both physical trauma and microbiologic insults. Our objectives in this grant are to (i) further define the mechanisms by which HGF can so effectively reverse formed scars, and (ii) determine whether the pro-regenerative effects of HGF on the corneal (surface) epithelium can also be extended to other important constituents of the tissue, including its nerves. How will this research advance ocular care and research as it applies to military and civilian populations? Ocular t
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110962
Entities
People
- Sunil K Chauhan
Organizations
- Schepens Eye Research Institute
- United States Army