Postnatal ocular growth is visually regulated so that, in the ideal circumstance, the eye grows to reach a balance between physical length and refractive power, allowing light from distant objects to be sharply focused on the retinal photoreceptors.
1 In the chick, glucagonergic amacrine cells are one of the most promising candidates for a direct role in the regulation of ocular growth by neural processing in the retina.
2 3 4 Visual conditions that prevent development of myopia stimulate expression of the immediate-early gene ZENK (zif/268, Egr-1) in glucagon-synthesizing amacrine cells, whereas conditions that promote excessive ocular growth stimulate little or no expression of ZENK.
2 3 There is also a concordant increase in the expression of mRNA for the glucagon precursor, proglucagon, during treatment with positive lenses.
5 This implies that an increase in the rate of synthesis and release of one or more proglucagon-derived peptides acts as a “stop” signal for ocular growth. Similarly, administration of exogenous glucagon or the synthetic glucagon agonist Lys
17,18,Glu
21-glucagon-NH
2 has been found to inhibit dose-dependently the axial elongation of the eye that would otherwise result from form deprivation (FD) or negative lens wear.
4 6 However, the concentration of glucagon necessary to inhibit ocular growth in response to FD (10
−5 M in 20 μL in the syringe; see Vessey et al.
7 ), although not taking into account dilution and distribution in the vitreous, is high compared with the affinity of the peptide for its receptors (
K d = 10
−9 M; see Ref.
8 ). Furthermore, the effects of glucagon receptor antagonists on ocular growth and refractive error development are weak and inconsistent.
4 6 Thus, although the activity of glucagon-containing amacrine cells is increased by visual stimuli that restrain eye growth, it is possible that glucagon is not an endogenous mediator of this signal or that glucagon (exogenous or endogenous) restrains growth via a related receptor rather than through the glucagon receptor itself.