Unearthing a therapeutic role for an ancient neuropeptide

A team of Harvard Medical School (MA, USA) researchers have used an evolutionarily conserved neuropeptide, α-melanocyte-stimulating hormone (α-MSH), to restore corneas in mice models of corneal endothelial disease.

Corneal endothelial diseases affect the corneal endothelial cells, which regulate corneal hydration. Dysregulation of hydration can result in swelling and potentially lead to blindness.

The lack of therapeutic options for corneal endothelial disease leaves corneal transplants as the common course of treatment.

However, transplants are not flawless; corneal endothelial cell loss following surgery can lead to complications like persistent corneal edema – a buildup of fluid in the cornea; which necessitates the development of alternative treatment options to remedy corneal endothelial cell loss from injury or disease.

A recent study has investigated alternative treatment options by exploring the therapeutic effect of α-MSH for treating a corneal injury. α-MSH is an evolutionarily conserved neuropeptide that acts on the melanocortin pathway in several tissues, acting on skin pigmentation, immunomodulation, reproductive function and energy homeostasis.

Researchers studied the local administration of α-MSH on mice models of injury-induced endothelial decompensation – a condition caused by the loss of the regulatory corneal endothelial cells, which results in corneal edema.

They observed multiple effects that underpin the hormone’s therapeutic potential: the prevention of corneal endothelial cell death, restoration of endothelial function, corneal cell regeneration and restoration of normal corneal thickness after an injury that would usually result in corneal thickening.

Lead investigator, Reza Dana, Director of the Cornea and Refractive Surgery Service at Mass Eye and Ear of the Harvard Medical School Department of Ophthalmology, concluded: “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. This study outlines the critical role played by neuropeptides in [corneal endothelial cell] maintenance and offers a novel perspective on their potential application in corneal endothelial regeneration.”

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