Efficacy of Neuropeptide Alpha-Melanocyte Stimulating Hormone (α-MSH) in Suppressing Corneal Edema Following Acute Injury

Abstract

Purpose : Corneal endothelial cells (CEnC) have minimal regenerative capacity, and insults to the endothelium may lead to significant corneal swelling. Studies have reported corneal nerve damage is associated with CEnC loss, suggesting nerves exert trophic effects on CEnC. Previously, we have demonstrated the cytoprotective function of the neuropeptide α-MSH against inflammatory and oxidative stress in CEnC ex vivo. Here, we investigate the efficacy of α-MSH in preventing corneal edema in a model of corneal endothelial injury.

Methods : Corneal injury was induced by transcorneal freezing in BALB/c mice (n=8/group) by placing a -196^oC 2 mm-diameter steel rod on the center of the cornea for 10 seconds. Beginning immediately after injury, mice received subconjunctival injections of 10µL of 10^-4 M α-MSH or PBS (control) twice weekly for a total of 8 weeks. Corneal edema was evaluated by assessing corneal opacity on slit lamp biomicroscopy and central corneal thickness (CCT) via optical coherence tomography. CEnC density and variability in cell size (polymegathism) and shape (hexagonality) were evaluated by in vivo confocal microscopy.

Results : In the untreated control group, transcorneal freezing led to significant corneal edema on d1 post-injury (CCT:180±28µm vs. baseline 101±2µm, P=0.007) which remained elevated 8wk after injury (186±14µm, P<0.001). There was a significant reduction in CEnC density (1821±42 cell/mm² vs. baseline 2954±67, P<0.001), an increase in polymegathism (CV: 41±3 vs. baseline 28±2, P=0.001) and a decline with a trend to significance in CEnC hexagonality (hexagonal cells%: 52±3 vs. baseline 59±4, P=0.079) at 8wk in the control group. In contrast, treatment with α-MSH restored normal (pre-injury) CCT (103±3µm, P=0.60). Further, compared to untreated control, subconjunctival injections of α-MSH led to clearer corneas with a significant reduction in edema (117±12, P=0.004), improved CEnC density (2209±132, P<0.001) and reduced CEnC polymegathism (CV:34±2, P=0.001). Restoration of normal CEnC morphology occurred earlier in the α-MSH treatment group compared to the control group.

Conclusions : Our results demonstrate that following corneal injury, treatment with α-MSH reverses corneal endothelial function by reducing CEnC loss. Our findings suggest a therapeutic role for α-MSH in preventing/restoring endothelial function following corneal injuries.

This is a 2021 ARVO Annual Meeting abstract.