Opposite effects of glucagon and insulin on compensation for spectacle lenses in chicks.
OBJECTIVE
Chick eyes compensate for the defocus imposed by positive or negative spectacle lenses. Glucagon may signal the sign of defocus. Do insulin (or IGF-1) and glucagon act oppositely in controlling eye growth, as they do in metabolic pathways and in control of retinal neurogenesis?


METHODS
Chicks, wearing lenses or diffusers or neither over both eyes, were injected with glucagon, a glucagon antagonist, insulin, or IGF-1 in one eye (saline in the other eye). Alternatively, chicks without lenses received insulin plus glucagon in one eye, and either glucagon or insulin in the fellow eye. Ocular dimensions, refractive errors, and glycosaminoglycan synthesis were measured over 2 to 4 days.


RESULTS
Glucagon attenuated the myopic response to negative lenses or diffusers by slowing ocular elongation and thickening the choroid; in contrast, with positive lenses, it increased ocular elongation to normal levels and reduced choroidal thickening, as did a glucagon antagonist. Insulin prevented the hyperopic response to positive lenses by speeding ocular elongation and thinning the choroid. In eyes without lenses, both insulin and IGF-1 speeded, and glucagon slowed, ocular elongation, but glucagon and insulin each increased the rate of thickening of the crystalline lens. When injected together, insulin blocked choroidal thickening by glucagon, at a dose that did not, by itself, thin the choroid.


CONCLUSIONS
Glucagon and insulin (or IGF-1) cause generally opposite modulations of eye growth, with glucagon mostly increasing choroidal thickness and insulin mostly increasing ocular elongation. These effects are mutually inhibitory and depend on the visual input.
Zhu
Xiaoying
X
Department of Biology, City College, CUNY, New York, New York 10031, USA. xiaoying@sci.ccny.cuny.edu
Wallman
Josh
J
D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects; D002645:Chickens; D002829:Choroid / Q000187:drug effects / Q000378:metabolism; D003261:Contact Lenses; D004195:Disease Models, Animal; D004338:Drug Combinations; D005123:Eye / Q000254:growth & development*; D005934:Glucagon / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006727:Hormone Antagonists / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D006956:Hyperopia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007267:Injections; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism; D009216:Myopia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D012590:Sclera / Q000378:metabolism; D012683:Sensory Deprivation
D004338:Drug Combinations; D006025:Glycosaminoglycans; D006727:Hormone Antagonists; D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; C080071:glucagonamide, desHis(1)-Glu(9)-; D007334:Insulin-Like Growth Factor I; D005934:Glucagon
Invest Ophthalmol Vis Sci. 2004 Feb;45(2):402-9
14744878
Exp Eye Res. 2001 Oct;73(4):533-46
11825024
Dev Biol. 2002 Nov 15;251(2):367-79
12435364
Dev Biol. 2000 Apr 15;220(2):197-210
10753510
Invest Ophthalmol Vis Sci. 2005 Nov;46(11):3932-42
16249466
Science. 1987 Jul 3;237(4810):73-7
3603011
Vis Neurosci. 2002 Nov-Dec;19(6):755-66
12688670
Invest Ophthalmol Vis Sci. 1990 Jun;31(6):1015-22
2162332
Curr Eye Res. 1990 Dec;9(12):1157-65
2091895
Endocr Rev. 1995 Feb;16(1):3-34
7758431
Vision Res. 1995 Jan;35(1):37-50
7839608
Invest Ophthalmol Vis Sci. 1997 Aug;38(9):1726-39
9286261
Graefes Arch Clin Exp Ophthalmol. 2007 Feb;245(2):267-75
16741711
Horm Metab Res. 1999 Feb-Mar;31(2-3):120-5
10226791
Curr Eye Res. 1992 Aug;11(8):767-82
1424721
Neuron. 2004 Aug 19;43(4):447-68
15312645
Exp Eye Res. 2007 May;84(5):951-9
17395180
Invest Ophthalmol Vis Sci. 2009 Jan;50(1):13-23
18599564
Dev Biol. 2008 May 1;317(1):196-212
18358467
Curr Eye Res. 2001 Sep;23(3):179-84
11803479
J Clin Endocrinol Metab. 1999 Dec;84(12):4349-54
10599687
Vision Res. 2002 Nov;42(24):2651-68
12445851
Invest Ophthalmol Vis Sci. 2000 Jun;41(7):1623-8
10845578
Invest Ophthalmol Vis Sci. 2002 Jan;43(1):246-52
11773038
Exp Eye Res. 2000 Apr;70(4):519-27
10866000
Comp Biochem Physiol A Mol Integr Physiol. 2003 Sep;136(1):95-112
14527633
Biochemistry. 1981 Dec 22;20(26):7345-50
6275879
Vision Res. 1987;27(7):1139-63
3660666
Acta Ophthalmol Scand. 2002 Apr;80(2):125-35
11952477
FEBS Lett. 1998 Oct 9;436(3):361-6
9801149
Development. 2002 May;129(9):2283-91
11959835
J Neuroendocrinol. 2006 Aug;18(8):611-20
16867182
J Neurosci. 2002 Nov 1;22(21):9387-98
12417664
Curr Eye Res. 1987 Aug;6(8):993-9
3665562
World J Surg. 2006 May;30(5):714-20
16680587
Exp Eye Res. 1997 Mar;64(3):465-76
9196399
Exp Eye Res. 1998 Feb;66(2):163-81
9533843
Invest Ophthalmol Vis Sci. 2005 Nov;46(11):3922-31
16249465
Brain Res Dev Brain Res. 2005 Jan 1;154(1):91-100
15617759
Vision Res. 1995 May;35(9):1175-94
7610579
J Neurochem. 1984 Dec;43(6):1522-6
6092540
Ophthalmic Physiol Opt. 1997 Jul;17(4):279-90
9390372
Vision Res. 2003 Jun;43(14):1519-31
12782066
J Neurosci. 2005 Nov 2;25(44):10157-66
16267223
Invest Ophthalmol Vis Sci. 2003 Feb;44(2):449-57
12556368
Curr Eye Res. 1997 Apr;16(4):320-6
9134320
Invest Ophthalmol Vis Sci. 2007 Jul;48(7):2957-66
17591860
Exp Eye Res. 1991 Jul;53(1):13-22
1879497
Nat Neurosci. 1999 Aug;2(8):706-12
10412059
J Orthop Res. 2001 Jul;19(4):712-9
11518283