Topical Calcitonin Gene-Related Peptide for Corneal Injury Prevention and Regeneration
Abstract
Rationale: Ocular trauma is common on the battlefield, comprising 13% of all body injuries. Mechanical injury such as corneal abrasion and scratches and chemical injury such as chemical splash are the most common sources of eye trauma and integral parts of explosion injuries, which account for more than 70% of eye injuries on the battlefield. The costs of eye injuries in the military from 2000-2010 were in excess of $2 billion per year. In civilian life, chemical injury to the eye increased by 20% in the past several years, with an average of $26.6 million per year in emergency departments’ charges only. More important than the economic impact is the lost vision and quality of life. Unfortunately, mechanical and chemical injuries often occur in both eyes, leaving otherwise able-bodied productive members of the military and society blind and disabled. Unmet Needs: The dome-shaped transparent cornea is the outermost protective layer of the eye. While mild scratch to the cornea such as an abrasion heals on its own, deeper scratches can cause scar formation in this transparent window of the eye and therefore cloud vision. When chemicals contact the eye, the eye must be flushed with large amounts of water, often requiring several liters to remove the chemicals completely. Other than flushing, there is no targeted treatment at time of injury. Despite proper flushing, corneal scarring can still occur. The situation is even worse on the battlefield with no access to clean water. If there is delayed evacuation of Warfighters, chemicals can stay on the eye for days, resulting in damage beyond treatment or repair. When the cornea is significantly scarred from mechanical or chemical injuries, a corneal transplant has to be performed. The transplanted cornea, however, does not have the smooth uniform shape of an intact cornea and is prone to rejection and failure with limited longevity. Therefore, an easy-to-use and effective therapy at time of injury will undoubtedly change the current standard of care for corneal injury. Research Idea: The cornea is the most sensitive tissue in our body due to its dense nerve endings, which are several hundredfold more than our skin. These nerves contain and release short proteins, and one of them is called calcitonin gene-related peptide (CGRP). CGRP has been shown to help skin heal. In our preliminary work, we gave CGRP as an eye drop daily to mice who had deep corneal scratches and found that CGRP helped the cornea heal faster with no significant scarring, swelling, or pain. We then collected these corneas and found that they had less tissue inflammation, fibrosis, and edema. We therefore hypothesize that giving CGRP as an eyedrop prevents corneal damage and restores corneal functions after mechanical and chemical injuries via anti-fibrotic, anti-inflammatory, and pro-regenerative mechanisms. Objectives/Aims: In this proposal, we will first examine whether giving CGRP immediately after mechanical and chemical injuries in mice can protect the cornea. We will then start CGRP treatment several days after injuries to determine if it can promote corneal regeneration. We will also use cultured cells to understand CGRP’s protective and anti-inflammatory functions. Last, we will examine the effects of CGRP treatment on tissue inflammation, corneal cell proliferation and death, and corneal nerves and blood vessels in the injured corneas. Impact: The proposed research will address current treatment gaps for ocular mechanical and chemical injuries by investigating the efficacy of a novel and naturally occurring neuropeptide. Once completed, this proposal will demonstrate the therapeutic potential of CGRP in treating acute mechanical and chemical injuries and potentially reversing tissue damage in the sub-acute phase. The proposed research will also advance the field of ocular trauma research including elucidating the role of corneal nerves and nerve-derived peptides in ey
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310951
Entities
People
- Jia Yin
Organizations
- Schepens Eye Research Institute
- United States Army