Skip to main content
Top
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 4/2004

01-04-2004 | Laboratory Investigation

The expression of myocilin during murine eye development

Authors: Carmen Knaupp, Cassandra Flügel-Koch, Andreas Goldwich, Andreas Ohlmann, Ernst R. Tamm

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 4/2004

Login to get access

Abstract

Purpose

To study the expression and localization of myocilin in the developing mouse eye. Myocilin is a 55- to 57-kDa secreted glycoprotein that is mutated in some forms of primary open-angle glaucoma.

Methods

The eyes of NMRI mice were studied from embryonic day (E) 14.5 to postnatal day (P) 21, and at 2–3 months of age. Immunohistochemistry was performed with antibodies against myocilin. The specificity of the antibodies was checked by two-dimensional gel electrophoresis. RNA was isolated from eyes at various ages, and the presence of myocilin mRNA was analyzed by northern blot hybridization.

Results

No immunostaining for myocilin was seen before E16.5. At around E17.5, a distinct positive immunoreactivity of optic nerve axons in the developing nerve fiber layer of the retina was observed. At P5–6, immunostaining appeared in perikarya of optic nerve ganglion cells. In the anterior eye, no immunoreactivity was observed until P10. At P12–14, the cells of the epithelial layers of ciliary body and iris, as well as the cells of the trabecular meshwork and iris stroma, became immunoreactive for myocilin. At that time, positive staining for myocilin was also seen in the corneal endothelium and in keratocytes of the corneal stroma. An essentially similar staining pattern was seen in adult eyes. Northern blot analysis for myocilin mRNA in RNA from developing mouse eyes was negative until P9. At P12, a distinct band was observed. A band with similar mobility, but somewhat more intense, was detected in mRNA from adult mouse eyes 2–3 months of age.

Conclusions

The onset of immunoreactivity for myocilin in the retina occurs in parallel with the maturation of optic nerve ganglion cells. In the anterior eye, the expression of myocilin is associated with the final development of those tissues that are directly involved in aqueous humor dynamics. The presence of myocilin might be important for proper function and structure of mature optic nerve ganglion cells and aqueous humor outflow.
Literature
1.
go back to reference Adam MF, Belmouden A, Binisti P, Brézin AP, Valtot F, Béchetoille A, Dascotte J-C, Copin B, Gomez L, Chaventre A, Bach J-F, Garchon H-J (1997) Recurrent mutations in a single exon encoding the evolutionarily conserved olfactomedin-homology domain of TIGR in familial open-angle glaucoma. Hum Mol Gen 12:2091–2097CrossRef Adam MF, Belmouden A, Binisti P, Brézin AP, Valtot F, Béchetoille A, Dascotte J-C, Copin B, Gomez L, Chaventre A, Bach J-F, Garchon H-J (1997) Recurrent mutations in a single exon encoding the evolutionarily conserved olfactomedin-homology domain of TIGR in familial open-angle glaucoma. Hum Mol Gen 12:2091–2097CrossRef
2.
go back to reference Ahmed F, Torrado M, Johnson E, Morrison J, Tomarev SI (2001) Changes in mRNA levels of the Myoc/Tigr gene in the rat eye after experimental elevation of intraocular pressure or optic nerve transection. Invest Ophthalmol Vis Sci 42:3165–3172PubMed Ahmed F, Torrado M, Johnson E, Morrison J, Tomarev SI (2001) Changes in mRNA levels of the Myoc/Tigr gene in the rat eye after experimental elevation of intraocular pressure or optic nerve transection. Invest Ophthalmol Vis Sci 42:3165–3172PubMed
3.
go back to reference Alward WL, Fingert JH, Coote MA, Johnson AT, Lerner SF, Junqua D, Durcan FJ, McCartney PJ, Mackey DA, Sheffield VC, Stone EM (1998) Clinical features associated with mutations in the chromosome 1 open-angle glaucoma gene. N England J Med 338:1022–1027CrossRef Alward WL, Fingert JH, Coote MA, Johnson AT, Lerner SF, Junqua D, Durcan FJ, McCartney PJ, Mackey DA, Sheffield VC, Stone EM (1998) Clinical features associated with mutations in the chromosome 1 open-angle glaucoma gene. N England J Med 338:1022–1027CrossRef
4.
go back to reference Cepko CL, Austin CP, Yang X, Alexiades M, Ezzeddine D (1996) Cell fate determination in the vertebrate retina. Proc Natl Acad Sci U S A 93:589–595CrossRefPubMed Cepko CL, Austin CP, Yang X, Alexiades M, Ezzeddine D (1996) Cell fate determination in the vertebrate retina. Proc Natl Acad Sci U S A 93:589–595CrossRefPubMed
5.
go back to reference Clark AF, Kawase K, English-Wright S, Lane D, Steely HT, Yamamoto T, Kitazawa Y, Kwon YH, Fingert JH, Swiderski RE, Mullins RF, Hageman GS, Alward WL, Sheffield VC, Stone EM (2001) Expression of the glaucoma gene myocilin (MYOC) in the human optic nerve head. FASEB J 15:1251–1253PubMed Clark AF, Kawase K, English-Wright S, Lane D, Steely HT, Yamamoto T, Kitazawa Y, Kwon YH, Fingert JH, Swiderski RE, Mullins RF, Hageman GS, Alward WL, Sheffield VC, Stone EM (2001) Expression of the glaucoma gene myocilin (MYOC) in the human optic nerve head. FASEB J 15:1251–1253PubMed
6.
go back to reference Danielson PE, Forss-Petter S, Battenberg EL, deLecea L, Bloom FE, Sutcliffe JG (1994) Four structurally distinct neuron-specific olfactomedin-related glycoproteins produced by differential promoter utilization and alternative mRNA splicing from a single gene. J Neurosci Res 38:468–478PubMed Danielson PE, Forss-Petter S, Battenberg EL, deLecea L, Bloom FE, Sutcliffe JG (1994) Four structurally distinct neuron-specific olfactomedin-related glycoproteins produced by differential promoter utilization and alternative mRNA splicing from a single gene. J Neurosci Res 38:468–478PubMed
7.
go back to reference Fautsch MP, Johnson DH (2001) Characterization of myocilin-myocilin interactions. Invest Ophthalmol Vis Sci 42:2324–2331PubMed Fautsch MP, Johnson DH (2001) Characterization of myocilin-myocilin interactions. Invest Ophthalmol Vis Sci 42:2324–2331PubMed
8.
go back to reference Fautsch MP, Bahler CK, Jewison DJ, Johnson DH (2000) Recombinant TIGR/MYOC increases outflow resistance in the human anterior segment. Invest Ophthalmol Vis Sci 41:4163–4168PubMed Fautsch MP, Bahler CK, Jewison DJ, Johnson DH (2000) Recombinant TIGR/MYOC increases outflow resistance in the human anterior segment. Invest Ophthalmol Vis Sci 41:4163–4168PubMed
9.
go back to reference Fingert JH, Heon E, Liebmann JM, Yamamoto T, Craig JE, Rait J, Kawase K, Hoh ST, Buys YM, Dickinson J, Hockey RR, Williams-Lyn D, Trope G, Kitazawa Y, Ritch R, Mackey DA, Alward WL, Sheffield VC, Stone EM (1999) Analysis of myocilin mutations in 1703 glaucoma patients from five different populations. Hum Mol Genet 8:899–905PubMed Fingert JH, Heon E, Liebmann JM, Yamamoto T, Craig JE, Rait J, Kawase K, Hoh ST, Buys YM, Dickinson J, Hockey RR, Williams-Lyn D, Trope G, Kitazawa Y, Ritch R, Mackey DA, Alward WL, Sheffield VC, Stone EM (1999) Analysis of myocilin mutations in 1703 glaucoma patients from five different populations. Hum Mol Genet 8:899–905PubMed
10.
go back to reference Fingert JH, Stone EM, Sheffield VC, Alward WL (2002) Myocilin glaucoma. Surv Ophthalmol 47:547–561CrossRefPubMed Fingert JH, Stone EM, Sheffield VC, Alward WL (2002) Myocilin glaucoma. Surv Ophthalmol 47:547–561CrossRefPubMed
11.
go back to reference Goldwich A, Ethier CR, Chan DW, Tamm ER (2003) Perfusion with the olfactomedin domain of myocilin does not affect outflow facility. Invest Ophthalmol Vis Sci 44:1953–1961CrossRefPubMed Goldwich A, Ethier CR, Chan DW, Tamm ER (2003) Perfusion with the olfactomedin domain of myocilin does not affect outflow facility. Invest Ophthalmol Vis Sci 44:1953–1961CrossRefPubMed
12.
go back to reference Jacobson N, Andrews M, Shepard AR, Nishimura D, Searby C, Fingert JH, Hageman G, Mullins R, Davidson BL, Kwon YH, Alward WL, Stone EM, Clark AF, Sheffield VC (2001) Non-secretion of mutant proteins of the glaucoma gene myocilin in cultured trabecular meshwork cells and in aqueous humor. Hum Mol Genet 10:117–125CrossRefPubMed Jacobson N, Andrews M, Shepard AR, Nishimura D, Searby C, Fingert JH, Hageman G, Mullins R, Davidson BL, Kwon YH, Alward WL, Stone EM, Clark AF, Sheffield VC (2001) Non-secretion of mutant proteins of the glaucoma gene myocilin in cultured trabecular meshwork cells and in aqueous humor. Hum Mol Genet 10:117–125CrossRefPubMed
13.
go back to reference Jurynec MJ, Riley CP, Gupta DK, Nguyen TD, McKeon RJ, Buck CR (2003) TIGR is upregulated in the chronic glial scar in response to central nervous system injury and inhibits neurite outgrowth. Mol Cell Neurosci 23:69–80CrossRefPubMed Jurynec MJ, Riley CP, Gupta DK, Nguyen TD, McKeon RJ, Buck CR (2003) TIGR is upregulated in the chronic glial scar in response to central nervous system injury and inhibits neurite outgrowth. Mol Cell Neurosci 23:69–80CrossRefPubMed
14.
go back to reference Karali A, Russell P, Stefani FH, Tamm ER (2000) Localization of myocilin/trabecular meshwork inducible glucocorticoid response protein in the human eye. Invest Ophthalmol Vis Sci 41:729–740PubMed Karali A, Russell P, Stefani FH, Tamm ER (2000) Localization of myocilin/trabecular meshwork inducible glucocorticoid response protein in the human eye. Invest Ophthalmol Vis Sci 41:729–740PubMed
15.
go back to reference Kubota R, Noda S, Wang Y, Minoshima S, Asakawa S, Kudoh J, Mashima Y, Oguchi Y, Shimizu N (1997) A novel myosin-like protein (myocilin) expressed in the connecting cilium of the photoreceptor: Molecular cloning, tissue expression and chromosomal mapping. Genomics 41:360–369PubMed Kubota R, Noda S, Wang Y, Minoshima S, Asakawa S, Kudoh J, Mashima Y, Oguchi Y, Shimizu N (1997) A novel myosin-like protein (myocilin) expressed in the connecting cilium of the photoreceptor: Molecular cloning, tissue expression and chromosomal mapping. Genomics 41:360–369PubMed
16.
go back to reference Nagano T, Nakamura A, Mori Y, Maeda M, Takami T, Shiosaka S, Takagi H, Sato M (1998) Differentially expressed olfactomedin-related glycoproteins (Pancortins) in the brain. Brain Res Mol Brain Res 53:13–23CrossRefPubMed Nagano T, Nakamura A, Mori Y, Maeda M, Takami T, Shiosaka S, Takagi H, Sato M (1998) Differentially expressed olfactomedin-related glycoproteins (Pancortins) in the brain. Brain Res Mol Brain Res 53:13–23CrossRefPubMed
17.
go back to reference Ohlmann A, Goldwich A, Flügel-Koch C, Fuchs AV, Schwager K, Tamm ER (2003) Secreted glycoprotein myocilin is a component of the myelin sheath in peripheral nerves. Glia 43:128–140CrossRefPubMed Ohlmann A, Goldwich A, Flügel-Koch C, Fuchs AV, Schwager K, Tamm ER (2003) Secreted glycoprotein myocilin is a component of the myelin sheath in peripheral nerves. Glia 43:128–140CrossRefPubMed
18.
go back to reference Ricard CS, Agapova OA, Salvador-Silva M, Kaufman PL, Hernandez MR (2001) Expression of myocilin/TIGR in normal and glaucomatous primate optic nerves. Exp Eye Res 73:433–447 Ricard CS, Agapova OA, Salvador-Silva M, Kaufman PL, Hernandez MR (2001) Expression of myocilin/TIGR in normal and glaucomatous primate optic nerves. Exp Eye Res 73:433–447
19.
go back to reference Russell P, Tamm ER, Grehn FJ, Picht G, Johnson M (2001) The presence and properties of myocilin in the aqueous humor. Invest Ophthalmol Vis Sci 42:983–986PubMed Russell P, Tamm ER, Grehn FJ, Picht G, Johnson M (2001) The presence and properties of myocilin in the aqueous humor. Invest Ophthalmol Vis Sci 42:983–986PubMed
20.
go back to reference Smith RS, Zabaleta A, Savinova OV, John SW (2001) The mouse anterior chamber angle and trabecular meshwork develop without cell death. B M C Dev Biol 1:3CrossRef Smith RS, Zabaleta A, Savinova OV, John SW (2001) The mouse anterior chamber angle and trabecular meshwork develop without cell death. B M C Dev Biol 1:3CrossRef
21.
go back to reference Stone EM, Fingert JH, Alward WLM, Nguyen TD, Polansky JR, Sunden SLF, Nishimura D, Clark AF, Nystuen A, Nichols BE, Mackey DA, Ritch R, Kalenak JW, Craven ER, Sheffield VC (1997) Identification of a gene that causes primary open angle glaucoma. Science 275:668–670PubMed Stone EM, Fingert JH, Alward WLM, Nguyen TD, Polansky JR, Sunden SLF, Nishimura D, Clark AF, Nystuen A, Nichols BE, Mackey DA, Ritch R, Kalenak JW, Craven ER, Sheffield VC (1997) Identification of a gene that causes primary open angle glaucoma. Science 275:668–670PubMed
22.
go back to reference Swiderski RE, Ying L, Cassell MD, Alward WL, Stone EM, Sheffield VC (1999) Expression pattern and in situ localization of the mouse homologue of the human MYOC (GLC1A) gene in adult brain. Brain Res Mol Brain Res 68:64–72CrossRefPubMed Swiderski RE, Ying L, Cassell MD, Alward WL, Stone EM, Sheffield VC (1999) Expression pattern and in situ localization of the mouse homologue of the human MYOC (GLC1A) gene in adult brain. Brain Res Mol Brain Res 68:64–72CrossRefPubMed
23.
go back to reference Swiderski RE, Ross JL, Fingert JH, Clark AF, Alward WL, Stone EM, Sheffield VC (2000) Localization of MYOC transcripts in human eye and optic nerve by in situ hybridization. Invest Ophthalmol Vis Sci 41:3420–3428PubMed Swiderski RE, Ross JL, Fingert JH, Clark AF, Alward WL, Stone EM, Sheffield VC (2000) Localization of MYOC transcripts in human eye and optic nerve by in situ hybridization. Invest Ophthalmol Vis Sci 41:3420–3428PubMed
24.
go back to reference Takahashi H, Noda S, Imamura Y, Nagasawa A, Kubota R, Mashima Y, Kudoh J, Oguchi Y, Shimizu N (1998) Mouse myocilin (Myoc) gene expression in ocular tissues. Biochem Biophys Res Commun 248:104–109CrossRefPubMed Takahashi H, Noda S, Imamura Y, Nagasawa A, Kubota R, Mashima Y, Kudoh J, Oguchi Y, Shimizu N (1998) Mouse myocilin (Myoc) gene expression in ocular tissues. Biochem Biophys Res Commun 248:104–109CrossRefPubMed
26.
go back to reference Tamm E, Russell P, Epstein DL, Johnson DH, Piatigorsky J (1999) Modulation of Myocilin/TIGR expression in human trabecular meshwork. Invest Ophthalmol Vis Sci 40:2577–2582PubMed Tamm E, Russell P, Epstein DL, Johnson DH, Piatigorsky J (1999) Modulation of Myocilin/TIGR expression in human trabecular meshwork. Invest Ophthalmol Vis Sci 40:2577–2582PubMed
27.
go back to reference Tamm ER, Russell P, Piatigorsky J (1999) Development and characterization of an immortal and differentiated murine trabecular meshwork cell line. Invest Ophthalmol Vis Sci 40:1392–1403PubMed Tamm ER, Russell P, Piatigorsky J (1999) Development and characterization of an immortal and differentiated murine trabecular meshwork cell line. Invest Ophthalmol Vis Sci 40:1392–1403PubMed
28.
go back to reference Tomarev SI, Wistow G, Raymond V, Dubois S, Malyukova I (2003) Gene expression profile of the human trabecular meshwork: NEIBank sequence tag analysis. Invest Ophthalmol Vis Sci 44:2588–2596CrossRefPubMed Tomarev SI, Wistow G, Raymond V, Dubois S, Malyukova I (2003) Gene expression profile of the human trabecular meshwork: NEIBank sequence tag analysis. Invest Ophthalmol Vis Sci 44:2588–2596CrossRefPubMed
29.
go back to reference Torrado M, Trivedi R, Zinovieva R, Karavanova I, Tomarev SI (2002) Optimedin: a novel olfactomedin-related protein that interacts with myocilin. Hum Mol Genet 11:1291–1301CrossRefPubMed Torrado M, Trivedi R, Zinovieva R, Karavanova I, Tomarev SI (2002) Optimedin: a novel olfactomedin-related protein that interacts with myocilin. Hum Mol Genet 11:1291–1301CrossRefPubMed
30.
go back to reference Young RW (1984) Cell death during differentiation of the retina in the mouse. J Comp Neurol 229:362–373PubMed Young RW (1984) Cell death during differentiation of the retina in the mouse. J Comp Neurol 229:362–373PubMed
31.
go back to reference Young RW (1985) Cell differentiation in the retina of the mouse. Anat Rec 212:199–205PubMed Young RW (1985) Cell differentiation in the retina of the mouse. Anat Rec 212:199–205PubMed
Metadata
Title
The expression of myocilin during murine eye development
Authors
Carmen Knaupp
Cassandra Flügel-Koch
Andreas Goldwich
Andreas Ohlmann
Ernst R. Tamm
Publication date
01-04-2004
Publisher
Springer-Verlag
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 4/2004
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-003-0851-1

Other articles of this Issue 4/2004

Graefe's Archive for Clinical and Experimental Ophthalmology 4/2004 Go to the issue