The Role of Alpha-MSH as a Modulator of Ocular Immunobiology Exemplifies Mechanistic Differences between Melanocortins and Steroids

ABSTRACT

Melanocortins are a highly conserved family of peptides and receptors that includes multiple proopiomelanocortin-derived peptides and five defined melanocortin receptors. The melanocortins have an important role in maintaining immune homeostasis and in suppressing inflammation. Within the healthy eye, the melanocortins have a central role in preventing inflammation and maintaining immune privilege. A central mediator of the anti-inflammatory activity is the non-steroidogenic melanocortin peptide alpha-melanocyte stimulating hormone. In this review we summarize the major findings of melanocortin regulation of ocular immunobiology with particular interest in the ability of melanocortin to induce immune tolerance and cytoprotection. The melanocortins have therapeutic potential because their mechanisms of action in regulating immunity are distinctly different from the actions of steroids.

Keywords:

• alpha-MSH
• eye
• glucocorticoids
• melanocortins

ACKNOWLEDGMENTS

Writing support for this manuscript was provided by Kelly P. Smith, and financial support for AWT was provided in part from the Massachusetts Lions Eye Research Foundation.

DECLARATION OF INTEREST

CMC and JY are employees of Mallinckrodt Pharmaceuticals, and AWT has been a consultant for Mallinckrodt Pharmaceuticals.