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Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology 2/2007

01.02.2007 | Laboratory Investigation

Glucagon-related peptides in the mouse retina and the effects of deprivation of form vision

verfasst von: Ute Mathis, Frank Schaeffel

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 2/2007

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Abstract

Background

In chickens, retinal glucagon amacrine cells play an important role in emmetropization, since they express the transcription factor ZENK (also known as NGFI-A, zif268, tis8, cef5, Krox24) in correlation with the sign of imposed image defocus. Pharmacological studies have shown that glucagon can act as a stop signal for axial eye growth, making it a promising target for pharmacological intervention of myopia. Unfortunately, in mammalian retina, glucagon itself has not yet been detected by immunohistochemical staining. To learn more about its possible role in emmetropization in mammals, we studied the expression of different members of the glucagon hormone family in mouse retina, and whether their abundance is regulated by visual experience.

Methods

Black wildtype C57BL/6 mice, raised under a 12/12 h light/dark cycle, were studied at postnatal ages between P29 and P40. Frosted hemispherical thin plastic shells (diffusers) were placed in front of the right eyes to impose visual conditions that are known to induce myopia. The left eyes remained uncovered and served as controls. Transversal retinal cryostat sections were single- or double-labeled by indirect immunofluorescence for early growth response protein 1 (Egr-1, the mammalian ortholog of ZENK), glucagon, glucagon-like peptide-2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP), peptide histidine isoleucine (PHI), growth hormone-releasing hormone (GHRH), pituitary adenylate cyclase-activating polypeptide (PACAP), secretin, and vasoactive intestinal polypeptide (VIP). In total, retinas of 45 mice were studied, 28 treated with diffusers, and 17 serving as controls.

Results

Glucagon itself was not detected in mouse retina. VIP, PHI, PACAP and GIP were localized. VIP was co-localized with PHI and Egr-1, which itself was strongly regulated by retinal illumination. Diffusers, applied for various durations (1, 2, 6, and 24 h) had no effect on the expression of VIP, PHI, PACAP, and GIP, at least at the protein level. Similarly, even if the analysis was confined to cells that also expressed Egr-1, no difference was found between VIP expression in eyes with diffusers and in eyes with normal vision.

Conclusions

Several members of the glucagon super family are expressed in mouse retina (although not glucagon itself), but their expression pattern does not seem to be regulated by visual experience.
Literatur
1.
Zurück zum Zitat Armstrong PE, Foy WL, Johnston CF, Shaw C, Murphy RF, Buchanan KD (1989) Peptide histidine isoleucine (PHI) immunoreactivity in the rat retina: identification and characterisation by radioimmunoassay, immunohistochemistry and high performance liquid chromatography. Regul Pept 25:325–332CrossRefPubMed Armstrong PE, Foy WL, Johnston CF, Shaw C, Murphy RF, Buchanan KD (1989) Peptide histidine isoleucine (PHI) immunoreactivity in the rat retina: identification and characterisation by radioimmunoassay, immunohistochemistry and high performance liquid chromatography. Regul Pept 25:325–332CrossRefPubMed
2.
Zurück zum Zitat Bitzer M, Schaeffel F (2002) Defocus-induced changes in Zenk expression in the chicken retina. Invest Ophthalmol Vis Sci 43:246–252PubMed Bitzer M, Schaeffel F (2002) Defocus-induced changes in Zenk expression in the chicken retina. Invest Ophthalmol Vis Sci 43:246–252PubMed
3.
Zurück zum Zitat Brand C, Burkhardt E, Schaeffel F, Choi JW, Feldkaemper MP (2005) Regulation of Egr-1, VIP, and Shh mRNA and Egr-1 protein in the mouse retina by light and image quality. Mol Vis 11:309–320PubMed Brand C, Burkhardt E, Schaeffel F, Choi JW, Feldkaemper MP (2005) Regulation of Egr-1, VIP, and Shh mRNA and Egr-1 protein in the mouse retina by light and image quality. Mol Vis 11:309–320PubMed
4.
Zurück zum Zitat Casini G, Molnar M, Brecha NC (1994) Vasoactive intestinal polypeptide/peptide histidine isoleucine messenger RNA in the rat retina: adult distribution and developmental expression. Neurosci 3:657–667CrossRef Casini G, Molnar M, Brecha NC (1994) Vasoactive intestinal polypeptide/peptide histidine isoleucine messenger RNA in the rat retina: adult distribution and developmental expression. Neurosci 3:657–667CrossRef
5.
Zurück zum Zitat Cellerino B, Arango-González G, Pinzón-Duarte G, Kohler K (2003) Brain-derived neurotrophic factor regulates expression of vasoactive intestinal polypeptide in retinal amacrine cells. J Comp Neurol 467:97–104CrossRefPubMed Cellerino B, Arango-González G, Pinzón-Duarte G, Kohler K (2003) Brain-derived neurotrophic factor regulates expression of vasoactive intestinal polypeptide in retinal amacrine cells. J Comp Neurol 467:97–104CrossRefPubMed
6.
Zurück zum Zitat Cho GJ, Ryu S, Kim YH, Cheon EW, Park JM, Kim HJ, Kang SS, Choi WS (2002) Upregulation of glucose-dependent insulinotropic polypeptide and its receptor in the retina of streptozotocin-induced diabetic rats. Curr Eye Res 6:381–388CrossRef Cho GJ, Ryu S, Kim YH, Cheon EW, Park JM, Kim HJ, Kang SS, Choi WS (2002) Upregulation of glucose-dependent insulinotropic polypeptide and its receptor in the retina of streptozotocin-induced diabetic rats. Curr Eye Res 6:381–388CrossRef
7.
Zurück zum Zitat Ekman R, Tornqvist K (1985) Glucagon and VIP in the retina. Invest Ophthalmol Vis Sci 26:1405–1409PubMed Ekman R, Tornqvist K (1985) Glucagon and VIP in the retina. Invest Ophthalmol Vis Sci 26:1405–1409PubMed
8.
Zurück zum Zitat Eriksen EF, Larsson L-I (1981) Neuropeptides in the retina: evidence for differential topographical localization. Peptides 2:153–157CrossRefPubMed Eriksen EF, Larsson L-I (1981) Neuropeptides in the retina: evidence for differential topographical localization. Peptides 2:153–157CrossRefPubMed
9.
Zurück zum Zitat Feldkaemper MP, Schaeffel F (2002) Evidence for a potential role of glucagon during eye growth regulation in chicks. Vis Neurosci 19:755–766CrossRefPubMed Feldkaemper MP, Schaeffel F (2002) Evidence for a potential role of glucagon during eye growth regulation in chicks. Vis Neurosci 19:755–766CrossRefPubMed
10.
Zurück zum Zitat Feldkaemper MP, Burkhardt E, Schaeffel F (2004) Localization and regulation of glucagon receptors in the chick eye and preproglucagon and glucagon receptor expression in the mouse eye. Exp Eye Res 79:321–329CrossRefPubMed Feldkaemper MP, Burkhardt E, Schaeffel F (2004) Localization and regulation of glucagon receptors in the chick eye and preproglucagon and glucagon receptor expression in the mouse eye. Exp Eye Res 79:321–329CrossRefPubMed
11.
Zurück zum Zitat Fernandez-Durango R, Sanchez D, Fernandez-Cruz A (1990) Identification of glucagon receptors in rat retina. J Neurochem 54:1233–1237PubMedCrossRef Fernandez-Durango R, Sanchez D, Fernandez-Cruz A (1990) Identification of glucagon receptors in rat retina. J Neurochem 54:1233–1237PubMedCrossRef
12.
Zurück zum Zitat Fischer AJ, McGuire JJ, Schaeffel F, Stell WK (1999) Light- and focus-dependent expression of the transcription factor ZENK in the chick retina. Nat Neurosci 2:706–712CrossRefPubMed Fischer AJ, McGuire JJ, Schaeffel F, Stell WK (1999) Light- and focus-dependent expression of the transcription factor ZENK in the chick retina. Nat Neurosci 2:706–712CrossRefPubMed
13.
Zurück zum Zitat Grimm A, Wenzel F, Hafezi C, Reme E (2000) Gene expression in the mouse retina: the effect of damaging light. Mol Vis 6:252–260PubMed Grimm A, Wenzel F, Hafezi C, Reme E (2000) Gene expression in the mouse retina: the effect of damaging light. Mol Vis 6:252–260PubMed
14.
Zurück zum Zitat Hannibal J, Ding JM, Chen D, Fahrenkrug J, Larsen PJ, Gilette MU, Mikkelsen JD (1997) Pituitary adenylate cyclase-activating polypeptide (PACAP) in the retinohypothalamic tract: a potential daytime regulator of the biological clock. J Neurosci 17:2637–2644PubMed Hannibal J, Ding JM, Chen D, Fahrenkrug J, Larsen PJ, Gilette MU, Mikkelsen JD (1997) Pituitary adenylate cyclase-activating polypeptide (PACAP) in the retinohypothalamic tract: a potential daytime regulator of the biological clock. J Neurosci 17:2637–2644PubMed
15.
Zurück zum Zitat Herbst H, Thier P (1996) Different effects of visual deprivation on vasoactive intestinal polypeptide (VIP)-containing cells in the retinas of juvenile and adult rats. Exp Brain Res 111:345–355CrossRefPubMed Herbst H, Thier P (1996) Different effects of visual deprivation on vasoactive intestinal polypeptide (VIP)-containing cells in the retinas of juvenile and adult rats. Exp Brain Res 111:345–355CrossRefPubMed
16.
Zurück zum Zitat Hui H, Zhao X, Perfetti R (2005) Structure and function studies of glucagon-like peptide-1 (GLP-1): the designing of a novel pharmacological agent for the treatment of diabetes. Diabetes Metab Res Rev 21:313–331CrossRefPubMed Hui H, Zhao X, Perfetti R (2005) Structure and function studies of glucagon-like peptide-1 (GLP-1): the designing of a novel pharmacological agent for the treatment of diabetes. Diabetes Metab Res Rev 21:313–331CrossRefPubMed
17.
Zurück zum Zitat Jaworski CJ, Tsai J-Y, John-Aryankalayil M, Cox C, Wawrousek E, Carper D (2005) Evidence for glucagon and GLP-2 in ocular tissues. Invest Ophthalmol Vis Sci 45 ARVO E-Abstract 5160 Jaworski CJ, Tsai J-Y, John-Aryankalayil M, Cox C, Wawrousek E, Carper D (2005) Evidence for glucagon and GLP-2 in ocular tissues. Invest Ophthalmol Vis Sci 45 ARVO E-Abstract 5160
18.
Zurück zum Zitat McBrien NA, Moghaddam HO, Reeder AP (1993) Atropine reduces experimental myopia and eye enlargement via a nonaccommodative mechanism. Invest Ophthalmol Vis Sci 34:205–215PubMed McBrien NA, Moghaddam HO, Reeder AP (1993) Atropine reduces experimental myopia and eye enlargement via a nonaccommodative mechanism. Invest Ophthalmol Vis Sci 34:205–215PubMed
19.
20.
Zurück zum Zitat Ohngemach S, Buck C, Simon P, Schaeffel F, Feldkaemper M (2004) Temporal changes of novel transcripts in the chicken retina following imposed defocus. Mol Vis 28:1019–1027 Ohngemach S, Buck C, Simon P, Schaeffel F, Feldkaemper M (2004) Temporal changes of novel transcripts in the chicken retina following imposed defocus. Mol Vis 28:1019–1027
21.
Zurück zum Zitat Ostrin LA, Frishman LJ, Glasser A (2004) Effects of pirenzepine on pupil size and accommodation in rhesus monkeys. Invest Ophthalmol Vis Sci 45:3620–3628CrossRefPubMed Ostrin LA, Frishman LJ, Glasser A (2004) Effects of pirenzepine on pupil size and accommodation in rhesus monkeys. Invest Ophthalmol Vis Sci 45:3620–3628CrossRefPubMed
22.
Zurück zum Zitat Pachter JA, Marshak DW, Lam DM, Fry KR (1989) A peptide histidine isoleucine/peptide histidine methionine-like peptide in the rabbit retina: colocalization with vasoactive intestinal peptide, synaptic relationships and activation of adenylate cyclase activity. Neuroscience 2:507–519CrossRef Pachter JA, Marshak DW, Lam DM, Fry KR (1989) A peptide histidine isoleucine/peptide histidine methionine-like peptide in the rabbit retina: colocalization with vasoactive intestinal peptide, synaptic relationships and activation of adenylate cyclase activity. Neuroscience 2:507–519CrossRef
23.
Zurück zum Zitat Raviola E, Wiesel TN, Lamk SL, Chetri A (1991) Increase of retinal vasoactive intestinal polypeptide (VIP) after neonatal lid fusion in the rhesus macaque. Invest Ophthalmol Vis Sci 32 [Suppl]:1203 Raviola E, Wiesel TN, Lamk SL, Chetri A (1991) Increase of retinal vasoactive intestinal polypeptide (VIP) after neonatal lid fusion in the rhesus macaque. Invest Ophthalmol Vis Sci 32 [Suppl]:1203
24.
Zurück zum Zitat Saw SM, Gazzard G, Au Eong KG, Koh D (2003) Utility values and myopia in teenage school students. Br J Ophthalmol 87:341–345CrossRefPubMed Saw SM, Gazzard G, Au Eong KG, Koh D (2003) Utility values and myopia in teenage school students. Br J Ophthalmol 87:341–345CrossRefPubMed
25.
Zurück zum Zitat Saw SM, Chua WH, Gazzard G, Koh D, Tan DT, Stone RA (2005) Eye growth changes in myopic children in Singapore. Br J Ophthalmol 89:1489–1494CrossRefPubMed Saw SM, Chua WH, Gazzard G, Koh D, Tan DT, Stone RA (2005) Eye growth changes in myopic children in Singapore. Br J Ophthalmol 89:1489–1494CrossRefPubMed
26.
Zurück zum Zitat Schaeffel F, Burkhardt E, Howland HC, Williams RW (2004) Measurement of refractive state and deprivation myopia in two strains of mice. Optom Vis Sci 81:99–110CrossRefPubMed Schaeffel F, Burkhardt E, Howland HC, Williams RW (2004) Measurement of refractive state and deprivation myopia in two strains of mice. Optom Vis Sci 81:99–110CrossRefPubMed
27.
Zurück zum Zitat Schmucker C, Schaeffel F (2004) In vivo biometry in the mouse eye with low coherence interferometry. Vision Res 44:2445–2456CrossRefPubMed Schmucker C, Schaeffel F (2004) In vivo biometry in the mouse eye with low coherence interferometry. Vision Res 44:2445–2456CrossRefPubMed
28.
Zurück zum Zitat Seki T, Shioda S, Nakai Y, Arimura A, Koide R (1998) Distribution and ultrastructural localization of pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor in the rat retina. Ann NY Acad Sci 865:408–411CrossRefPubMed Seki T, Shioda S, Nakai Y, Arimura A, Koide R (1998) Distribution and ultrastructural localization of pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor in the rat retina. Ann NY Acad Sci 865:408–411CrossRefPubMed
29.
Zurück zum Zitat Seki T, Shioda S, Izumi S, Arimura A, Koide R (2000) Electron microscopic observation of pituitary adenylate cyclase-activating polypeptide (PACAP)-containing neurons in the rat retina. Peptides 21:109–113CrossRefPubMed Seki T, Shioda S, Izumi S, Arimura A, Koide R (2000) Electron microscopic observation of pituitary adenylate cyclase-activating polypeptide (PACAP)-containing neurons in the rat retina. Peptides 21:109–113CrossRefPubMed
30.
Zurück zum Zitat Sherwood NM, Krueckl SL, McRory JE (2000) The origin and function of the pituitary adenylate cyclase- activating polypeptide (PACAP) glucagon superfamily. Endocr Rev 21:619–670CrossRefPubMed Sherwood NM, Krueckl SL, McRory JE (2000) The origin and function of the pituitary adenylate cyclase- activating polypeptide (PACAP) glucagon superfamily. Endocr Rev 21:619–670CrossRefPubMed
31.
Zurück zum Zitat Shih YF, Chen CH, Chou AC, Ho TC, Lin LL, Hung PT (1999) Effects of different concentrations of atropine on controlling myopia in myopic children. J Ocul Pharmacol Ther 15:85–90PubMedCrossRef Shih YF, Chen CH, Chou AC, Ho TC, Lin LL, Hung PT (1999) Effects of different concentrations of atropine on controlling myopia in myopic children. J Ocul Pharmacol Ther 15:85–90PubMedCrossRef
32.
Zurück zum Zitat Siatkowski RM, Cotter S, Miller JM, Scher CA, Crockett RS, Novack GD (2004) Safety and efficacy of 2% pirenzepine ophthalmic gel in children with myopia: a 1-year, multicenter, double-masked, placebo-controlled parallel study. Arch Ophthalmol 122:1667–1674CrossRefPubMed Siatkowski RM, Cotter S, Miller JM, Scher CA, Crockett RS, Novack GD (2004) Safety and efficacy of 2% pirenzepine ophthalmic gel in children with myopia: a 1-year, multicenter, double-masked, placebo-controlled parallel study. Arch Ophthalmol 122:1667–1674CrossRefPubMed
33.
Zurück zum Zitat Stanke JJ, Fischer AJ (2005) Developmental of cholinergic amacrine cells in the chicken retina. Invest Ophthalmol Vis Sci 45 ARVO E-Abstract 559 Stanke JJ, Fischer AJ (2005) Developmental of cholinergic amacrine cells in the chicken retina. Invest Ophthalmol Vis Sci 45 ARVO E-Abstract 559
34.
Zurück zum Zitat Terubayashi H, Tsuto HT, Fukui K, Obata HL, Okamura H, Gujisawa H, Itoi M, Yanaihara C, Yanaihara N, Ibata J (1983) VIP (vasoactive intestinal polypeptide)-like immunoreactive amacrine cells in the retina of the rat. Exp Eye Res 36:743–749CrossRefPubMed Terubayashi H, Tsuto HT, Fukui K, Obata HL, Okamura H, Gujisawa H, Itoi M, Yanaihara C, Yanaihara N, Ibata J (1983) VIP (vasoactive intestinal polypeptide)-like immunoreactive amacrine cells in the retina of the rat. Exp Eye Res 36:743–749CrossRefPubMed
35.
Zurück zum Zitat Tigges M, Iuvone PM, Fernandes A, Sugrue MF, Mallorga PJ, Laties AM, Stone RA (1999) Effects of muscarinic cholinergic receptor antagonists on postnatal eye growth of rhesus monkeys. Optom Vis Sci 76:397–407PubMedCrossRef Tigges M, Iuvone PM, Fernandes A, Sugrue MF, Mallorga PJ, Laties AM, Stone RA (1999) Effects of muscarinic cholinergic receptor antagonists on postnatal eye growth of rhesus monkeys. Optom Vis Sci 76:397–407PubMedCrossRef
36.
Zurück zum Zitat Tornqvist K, Uddman R, Sundler F, Ehinger B (1982) Somatostatin and VIP neurons in the retina of different species. Histochemistry 76:137–152CrossRefPubMed Tornqvist K, Uddman R, Sundler F, Ehinger B (1982) Somatostatin and VIP neurons in the retina of different species. Histochemistry 76:137–152CrossRefPubMed
37.
Zurück zum Zitat Truong HT, Cottrial CL, Gentle A, McBrien NA (2002) Pirenzepine affects scleral metabolic changes in myopia through a non-toxic mechanism. Ophthalmology 110:1069–1070 Truong HT, Cottrial CL, Gentle A, McBrien NA (2002) Pirenzepine affects scleral metabolic changes in myopia through a non-toxic mechanism. Ophthalmology 110:1069–1070
38.
Zurück zum Zitat Unson CG, Cypess AM, Wu CR, Goldsmith PK, Merifield RB, Sakmar TP (1996) Antibodies against specific extracellular epitopes of the glucagon receptor block glucagon binding. Proc Natl Acad Sci USA 93:310–315CrossRefPubMed Unson CG, Cypess AM, Wu CR, Goldsmith PK, Merifield RB, Sakmar TP (1996) Antibodies against specific extracellular epitopes of the glucagon receptor block glucagon binding. Proc Natl Acad Sci USA 93:310–315CrossRefPubMed
39.
Zurück zum Zitat Vessey KA, Lencses KA, Rushforth DA, Hruby VJ, Stell WK (2005) Glucagon receptor agonists and antagonists affect the growth of the chick eye: a role for glucagonergic regulation of emmetropization? Invest Ophthalmol Vis Sci 46:3922–3931CrossRefPubMed Vessey KA, Lencses KA, Rushforth DA, Hruby VJ, Stell WK (2005) Glucagon receptor agonists and antagonists affect the growth of the chick eye: a role for glucagonergic regulation of emmetropization? Invest Ophthalmol Vis Sci 46:3922–3931CrossRefPubMed
40.
Zurück zum Zitat Vessey KA, Rushforth DA, Stell WK (2005) Glucagon- and secretin-related peptides differentially alter ocular growth and the development of form-deprivation myopia in chicks. Invest Ophthalmol Vis Sci 46:3932–3942CrossRefPubMed Vessey KA, Rushforth DA, Stell WK (2005) Glucagon- and secretin-related peptides differentially alter ocular growth and the development of form-deprivation myopia in chicks. Invest Ophthalmol Vis Sci 46:3932–3942CrossRefPubMed
41.
42.
Zurück zum Zitat Zhong X, Ge J, Smith EL III, Stell WK (2004) Image defocus modulates activity of bipolar and amacrine cells in macaque retina. Invest Ophthalmol Vis Sci 45:2065–2074CrossRefPubMed Zhong X, Ge J, Smith EL III, Stell WK (2004) Image defocus modulates activity of bipolar and amacrine cells in macaque retina. Invest Ophthalmol Vis Sci 45:2065–2074CrossRefPubMed
Metadaten
Titel
Glucagon-related peptides in the mouse retina and the effects of deprivation of form vision
verfasst von
Ute Mathis
Frank Schaeffel
Publikationsdatum
01.02.2007
Verlag
Springer-Verlag
Erschienen in
Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 2/2007
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-006-0282-x

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