Abstract
Abstract: :
Purpose: Glucagon–synthesizing amacrine cells in chicks are stimulated by visual conditions that prevent myopia development but not by conditions that promote excessive ocular growth. In addition, exogenous glucagon inhibits myopia progression, but the endogenous peptide derived from the glucagon precursor (proglucagon) that regulates eye growth is unclear. The aim of this study was to determine which of the proglucagon–derived peptides plays a role in ocular growth control. Methods: White Leghorn cockerels, kept under a 12:12 hr L:D cycle, were monocularly form–deprived (FD) on day 6 after hatching (P6). Chicks received a total of 5 intravitreal injections of 20µL of peptide solution or saline into FD eyes and saline into open eyes every 48hrs from P7. Peptides tested (human glucagon [1–29], oxyntomodulin, miniglucagon and glucagon–like peptide 2 (GLP–2); chicken GLP–1) were delivered at concentrations ranging ∼10–9 to 10–5M in the vitreous. At P16, chick eyes were refracted, measured by high–resolution A–scan ultrasonography, removed and weighed (n=6–8 for each peptide and dose). Results: (1) As reported previously, glucagon prevented excessive ocular elongation and myopia with an ED50<font face="symbol">@</font>10–6M, for refractive error, vitreal chamber depth, axial length and eye weight. Glucagon also induced choroidal thickening. (2) Oxyntomodulin affected these parameters similarly and significantly with an ED50<font face="symbol">@</font>–10–7M. (3) Miniglucagon and GLP–2 had no significant effect on induced myopia, even at 10–5M. (4) GLP–1, in contrast, enhanced myopic refractive error in FD eyes at 10–5M by increasing anterior chamber depth. Conclusions: (1) Prevention of experimental myopia by exogenous glucagon is mediated by receptors specific for glucagon or oxyntomodulin, indicating that one of these peptides is the most probable endogenous mediator of ocular growth–inhibition. (2) GLP–1 has separate and distinctive effects on ocular growth and refractive error development. (3) The role of proglucagon–synthesizing amacrine cells in emmetropization may be altered by selective processing of proglucagon to regulate the kinds of peptides that are released.
Keywords: myopia • pharmacology • neuropeptides