Glucagon- and Secretin-Related Peptides Differentially Alter Ocular Growth and the Development of Form-Deprivation Myopia in Chicks

Abstract

Exogenous glucagon inhibits the induction of myopia in chicks, but the endogenous peptide and receptor that regulate eye growth are unknown. The purpose of this study was to determine which peptides and receptors in the glucagon-secretin family play a role in the control of ocular growth. The effect of intravitreally injected peptides on the development of form-deprivation (FD) myopia and on the growth of eyes with unrestricted vision was determined by refraction and A-scan ultrasonography. Chicks received three injections, one every 48 hours, of secretin-related peptides (porcine secretin, human peptide histidine-isoleucine-amide-27, vasoactive intestinal peptide [VIP], VIP fragment 6-28, or pituitary adenylate cyclase-activating polypeptide; 10(-8)-10(-4) M in 20 microL) or five injections of proglucagon-derived peptides (human glucagon, oxyntomodulin, miniglucagon, or glucagon-like peptide [GLP]-2 or chicken GLP-1). Immunohistochemistry was used to detect proglucagon-derived peptides in the eye. Secretin-related peptides had no effect on FD myopia, whereas some proglucagon-derived peptides did. Both glucagon and oxyntomodulin dose-dependently inhibited development of myopia, primarily by inhibition of vitreous chamber elongation (EC(50) = 10(-4) M and 10(-5.5) M, respectively). GLP-1 increased deprivation-induced myopic refractive error by altering anterior chamber development. None of the peptides significantly affected refractive error in eyes with unrestricted vision, although changes in anterior and posterior eye growth were observed in response to glucagon, oxyntomodulin, GLP-1, and miniglucagon. Immunoreactivity for miniglucagon and GLP-1 was colocalized in glucagon-immunoreactive amacrine cells. Prevention of experimental myopia by exogenous glucagon is mediated by receptors selective for glucagon and oxyntomodulin, indicating that glucagon-like peptides and receptors are probable endogenous retinal regulators of the development of myopia.