Myocilin Expression in the Astrocytes of the Optic Nerve Head

Noda, Shinichi; Mashima, Yukihiko; Obazawa, Minoru; Kubota, Ryo; Oguchi, Yoshihisa; Kudoh, Jun; Minoshima, Shinsei; Shimizu, Nobuyoshi

doi:10.1006/bbrc.2000.3591

Cited by 31 publications

(26 citation statements)

References 20 publications

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“…Myocilin was the first molecule discovered to be linked with primary open angle glaucoma (POAG), a blinding disease characterized by progressive loss of retinal ganglion cells. It was reported that optic nerve head astrocytes constitutively express myocilin in vivo (Noda et al 2000;Ricard et al 2001). In the present study, a 5-fold increase in Myocilin gene-expression was found in type II astrocytes as compared to OPCs, confirming the previous finding.…”

Section: Candidate Genes That May Contribute To Type II Astrocyte Fatsupporting

confidence: 92%

Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes

Wang

Zhou

et al. 2011

Tohoku J. Exp. Med.

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Oligodendrocyte precursor cells (OPCs) are bipotential progenitor cells that can differentiate into myelin-forming oligodendrocytes or functionally undetermined type II astrocytes. Transplantation of OPCs is an attractive therapy for demyelinating diseases. However, due to their bipotential differentiation potential, the majority of OPCs differentiate into astrocytes at transplanted sites. It is therefore important to understand the molecular mechanisms that regulate the transition from OPCs to oligodendrocytes or astrocytes. In this study, we isolated OPCs from the spinal cords of rat embryos (16 days old) and induced them to differentiate into oligodendrocytes or type II astrocytes in the absence or presence of 10% fetal bovine serum, respectively. RNAs were extracted from each cell population and hybridized to GeneChip with 28,700 rat genes. Using the criterion of fold change > 4 in the expression level, we identified 83 genes that were up-regulated and 89 genes that were down-regulated in oligodendrocytes, and 92 genes that were up-regulated and 86 that were down-regulated in type II astrocytes compared with OPCs. The up-regulated genes, such as activating transcription factor 3 and myelin basic protein in oligodendrocytes or claudin 11 in type II astrocytes, might contribute to OPC differentiation and represent constitutive components of oligodendrocytes or type II astrocytes. The down-regulated genes in both oligodendrocytes and type II astrocytes, such as transcription factor 19, might be involved in maintaining self-renewal and/or represent the property of OPCs. These results provide new insights into the elucidation of the molecular mechanisms, by which OPCs differentiate to oligodendrocytes or type II astrocytes.

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Section: Candidate Genes That May Contribute To Type II Astrocyte Fatsupporting

confidence: 92%

Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes

Wang

Zhou

et al. 2011

Tohoku J. Exp. Med.

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“…Recent studies have shown that myocilin, also known as trabecular meshwork-inducible glucocorticoid response protein (TIGR), is expressed in astrocytes of the optic nerve head at the lamina cribrosa (Karali et al, 2000;Noda et al, 2000;Clark et al, 2001a;Ricard et al, 2001) and is a component of the myelin sheath that surrounds postlaminar optic nerve axons (Ricard et al, 2001). Mutations in the myocilin gene are responsible for some forms of primary open-angle glaucoma, a neurodegenerative disease that is characterized by a continuous loss of optic nerve axons (Stone et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Secreted glycoprotein myocilin is a component of the myelin sheath in peripheral nerves

Ohlmann

Goldwich

Flügel-Koch

et al. 2003

Glia

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The structure of the myelin sheath in peripheral nerves requires the expression of a specific set of proteins. In the present study, we report that myocilin, a member of the olfactomedin protein family, is a component of the myelin sheath in peripheral nerves. Myocilin is a secreted glycoprotein that forms multimers and contains a leucine zipper and an olfactomedin domain. Mutations in myocilin are responsible for some forms of glaucoma, a neurodegenerative disease that is characterized by a continuous loss of optic nerve axons. Myocilin mRNA was detected by Northern blotting in RNA from the rat sciatic and ophthalmic nerves. By one- and two-dimensional gel electrophoresis of proteins from the rat and human sciatic nerves, myocilin was found to migrate at an isoelectric point (pI) of 5.2-5.3 and a molecular weight of 55-57 kDa. Immunohistochemistry showed immunoreactivity for myocilin in paranodal terminal loops of the nodes of Ranvier and outer mesaxons and basal/abaxonal regions of the myelin sheath. Double-labeling experiments with antibodies against myelin basic protein showed no overlapping, while overlapping immunoreactivity was observed with antibodies against myelin-associated glycoprotein. The expression of myocilin in the sciatic nerve became detectable at postnatal day (P) 15 and reached adult levels at P20. No or minor expression of myocilin mRNA was found in brain, spinal cord, and optic nerve. mRNA of myocilin was detected in schwannoma cells in situ, but at considerably lower levels than in myelinated nerves. Myocilin might significantly contribute to the structure of the myelin sheath in peripheral nerves.

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“…In recent studies, intracellular as well as extracellular expression of myocilin has been reported in astrocytes and lamina cribrosa cells of the optic nerve head [14,21]. These observations suggest the possible involvement of myocilin in the glaucomatous damage of the optic nerve head.…”

Section: Discussionmentioning

confidence: 87%

“…according to the following criteria: presence of typical optic disk damage with glaucomatous cupping and loss of the neuroretinal rim; reproducible visual field defect compatible with glaucomatous cupping; untreated peak IOP that was ^21 mm Hg at all times, including both the 5 baseline measurements and the diurnal testing (every 3 h from 6.00 to 24.00 h); open drainage angles on gonioscopy, and the absence of any secondary cause for glaucomatous optic neuropathy, such as a previously raised IOP following trauma, or a period of steroid administration or uveitis. The demographic features of 80 NTG patients were: 44 men and 36 women, mean age at the initial diagnosis was 54.0 B 12.8 years, mean highest diurnal IOP was 16.3 B 2.8 mm Hg (range [11][12][13][14][15][16][17][18][19][20][21], and the mean values of the mean deviation (MD) and corrected pattern standard deviation (CPSD) on Humphrey perimetry (program 30-2) were -7.59 B 6.98 dB and -6.52 B 4.87 dB, respectively.…”

Section: Patientsmentioning

confidence: 99%

Variants of the Myocilin Gene in Japanese Patients with Normal-Tension Glaucoma

Izumi

Mashima²,

Obazawa³

et al. 2003

Ophthalmic Res

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Myocilin (MYOC) mutations are associated with juvenile- and adult-onset primary open-angle glaucoma (POAG). The purpose of this study was to determine whether MYOC gene mutations are associated with normal-tension glaucoma (NTG). The prevalence of MYOC mutations was determined in 80 Japanese NTG patients and 100 control subjects. In addition, the expression of mutant MYOC was determined by transforming COS-1 cells with five myocilin variants (R158Q, D208E, I360N, A363T, and I477S) and examining whether myocilin was present in the cultured cells and/or the culture medium by western blotting. Six different nucleotide sequence variants, R46Stop, R76K, R158Q, D208E, A488A, and one in the 3′ non-coding region, were identified in 80 NTG patients. Variants in codon 46 (R46Stop), codon 158 (R158Q), and codon 488 (A488A) were not found in the 100 normal controls. The frequency of other sequence changes (R76K, D208E, and 3′ non-coding) in NTG patients did not differ significantly from the frequencies in the control subjects. COS-1 cells transfected with the wild type, R158Q, or D208E variants secreted myocilin into the culture medium. On the other hand, the detected myocilin was significantly reduced in the medium of cells transfected with the I360N, A363T, or I477S variants that were previously identified as mutations for POAG. Definitive evidence of MYOC variants associated with NTG was not found.

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Myocilin Expression in the Astrocytes of the Optic Nerve Head

Cited by 31 publications

References 20 publications

Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes

Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes

Secreted glycoprotein myocilin is a component of the myelin sheath in peripheral nerves

Variants of the Myocilin Gene in Japanese Patients with Normal-Tension Glaucoma

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