Study highlights treatment option for corneal endothelial disease, reducing need for corneal transplants

(Image Credit: AdobeStock/Herr Hesse)

A team of researchers from Harvard Medical School has found that administration of the neuropeptide α–melanocyte–stimulating hormone (α-MSH) promotes corneal healing and restores normal eye function to an otherwise degenerating and diseased cornea by providing protection against cell death and promoting cell regeneration.

Their study was published recently in the American Journal of Pathology.¹

As a result of a lack of available medical therapy, patients suffering from corneal endothelial disease, which leads to corneal swelling and potentially blindness, commonly require corneal transplantation. Corneal transplantation is the most common type of transplant performed.

According to the study, there is an unmet need for safe and effective medical strategies for the prevention and reversal of persistent corneal edema, according to the investigators at Mass Eye and Ear of the Harvard Medical School Department of Ophthalmology. There also is an increasing need for the development of efficacious treatment for preventing and potentially reversing, corneal edema due to corneal endothelial cell (CenC) loss following corneal injury.

“Corneal endothelial cells regulate corneal hydration and maintain tissue transparency through their barrier and pump function,” the researchers wrote. “However, these cells exhibit limited regenerative capacity following injury.”

In the study, researchers looked at the effect of local administration of α-MSH on persistent corneal edema and endothelial regeneration in an established model of injury-induced endothelial decompensation. The results show the impressive therapeutic potential of promoting the melanocortin pathway using α-MSH, thus opening new avenues of therapy.¹

Researchers at Harvard Medical School have demonstrated the potent therapeutic effects of administration of the neuropeptide α-melanocyte–stimulating hormone (α-MSH) through melanocortin receptor agonism, providing compelling evidence for the therapeutic potential of this pathway for a wide array of eye disorders. CEnC, corneal endothelial cells; PBS, phosphate-buffered saline. (Image credit: The American Journal of Pathology)

Lead investigator Reza Dana, MD, MSc, MPH, director of the Cornea and Refractive Surgery Service at Mass Eye and Ear, and Claes H. Dohlman Professor of Ophthalmology at Harvard Medical School, highlighted the team’s data in a news release.²

"Our data, demonstrating the potent therapeutic effects of α-MSH through melanocortin receptor agonism, provide compelling evidence for the therapeutic potential of this pathway for a wide array of ocular disorders such as Fuchs Dystrophy, a common disease and indication for corneal transplantation, as well as other disorders of the corneal endothelium that lead to corneal swelling," Dana said in the news release.

Moreover, according to the researchers, α-MSH is an evolutionarily conserved neuropeptide derived from the proteolysis of the pro-opiomelanocortin and exerts an array of functions through different melanocortin receptors expressed in various tissues.¹ Findings in this seminal study show that administration of α-MSH:

• Prevents corneal endothelial cell death
• Restores normal endothelial function
• Permits the cornea to resume normal thickness after a severe injury that normally leads to corneal thickening
• Causes corneal cells to regenerate

Options to head off corneal edema following ocular injury are limited and currently include topical hypertonic saline and topical anti-inflammatory drugs. However, these interventions have limited efficacy, and they do not prevent CEnC decompensation.

Dana said the research highlights potential options.

“The findings of our study suggest the therapeutic potential of α-MSH, or analogs that work by activating the melanocortin receptor system, in management of pathologies where there is a risk of corneal endothelial dysfunction, such as corneal injury or intraocular surgery,” Dana concluded in the news release. “This study outlines the critical role played by neuropeptides in CEnC maintenance and offers a novel perspective on their potential application in corneal endothelial regeneration."

Reference

1. Reza Dana, Hamid, Alemi, Shudan Wang, Tomas Blanco, Ula V. Jurkunas, Jia, Yin, et.al. The Neuropeptide α-Melanocyte–Stimulating Hormone Prevents Persistent Corneal Edema Following Injury. Cells. Published October 10, 2023. Accessed January 3, 2024. DOI: 10.1016/j.ajaqpth.2023.09.007.

2. Pioneering study indicates a potential treatment for corneal endothelial disease, reducing the need for corneal transplants. EurekAlert! Accessed January 3, 2024. https://www.eurekalert.org/news-releases/1030089