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Changes in retinal gene expression in proliferative vitreoretinopathy: glial cell expression of HB-EGF.
Mol Vis. 2005 Jun 10; 11:397-413.MV

Abstract

PURPOSE

To compare the gene expression pattern of control postmortem retinas with retinas from patients with proliferative vitreoretinopathy (PVR), to determine the expression of the heparin binding epidermal growth factor-like growth factor (HB-EGF) by glial cells in fibroproliferative membranes, and to examine whether cells of the human Müller cell line, MIO-M1, respond to HB-EGF with proliferation, migration, and secretion of the vascular endothelial growth factor (VEGF).

METHODS

To identify genes that were differently expressed in PVR and control retinas, the RNA from the neural retinas of seven postmortem donors and of two patients with PVR were analyzed for differential gene expression, by hybridization of labeled cRNA probes to an Affymetrix human genome microarray set. The results were validated by real time PCR experiments investigating RNA from 6 postmortem retinas and 4 PVR retinas. Epiretinal PVR membranes were immunohistochemically stained for colocalization of HB-EGF and the glial cell marker, glial fibrillary acidic protein (GFAP). The HB-EGF evoked proliferation of cultured Müller cells was investigated by a bromodeoxyuridine immunoassay, chemotaxis was assessed with a migration assay, and the release of VEGF was evaluated by ELISA.

RESULTS

Out of the 12,600 genes and expressed sequence tags investigated, the levels of 80 showed an increased expression, and 21 were expressed at decreased levels, in the retinas of PVR patients compared to the control retinas. The upregulated signals include genes for nuclear and cell cycle related proteins, extracellular secretory proteins, cytosolic signaling proteins, and proteins of the membrane and the extracellular matrix. The genes of the hepatocyte growth factor and of HB-EGF were found to be expressed in PVR retinas but not in control retinas. In epiretinal membranes of patients with PVR, HB-EGF immunoreactivity partially colocalized with GFAP. In cultured Müller cells, HB-EGF stimulated both proliferation and chemotaxis, and the secretion of VEGF, via activation of the extracellular signal regulated kinases 1 and 2 and of the phosphatidylinositol-3 kinase.

CONCLUSIONS

The development of PVR is accompanied by complex changes of the gene expression in the neural retina, with an upregulation of genes that support cell proliferation, cell signaling, cell motility, and extracellular matrix remodeling. HB-EGF is one of the factors that are significantly upregulated in PVR retinas. HB-EGF expression in fibroproliferative tissue and its stimulatory effect on glial cell proliferation, chemotaxis, and VEGF secretion suggest that HB-EGF may be a factor mediating glial cell responses during PVR.

Authors+Show Affiliations

Department of Ophthalmology, University Eye Hospital, University of Leipzig, Leipzig, Germany. hollbm@medizin.uni-leipzig.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15988409

Citation

Hollborn, Margrit, et al. "Changes in Retinal Gene Expression in Proliferative Vitreoretinopathy: Glial Cell Expression of HB-EGF." Molecular Vision, vol. 11, 2005, pp. 397-413.
Hollborn M, Tenckhoff S, Jahn K, et al. Changes in retinal gene expression in proliferative vitreoretinopathy: glial cell expression of HB-EGF. Mol Vis. 2005;11:397-413.
Hollborn, M., Tenckhoff, S., Jahn, K., Iandiev, I., Biedermann, B., Schnurrbusch, U. E., Limb, G. A., Reichenbach, A., Wolf, S., Wiedemann, P., Kohen, L., & Bringmann, A. (2005). Changes in retinal gene expression in proliferative vitreoretinopathy: glial cell expression of HB-EGF. Molecular Vision, 11, 397-413.
Hollborn M, et al. Changes in Retinal Gene Expression in Proliferative Vitreoretinopathy: Glial Cell Expression of HB-EGF. Mol Vis. 2005 Jun 10;11:397-413. PubMed PMID: 15988409.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in retinal gene expression in proliferative vitreoretinopathy: glial cell expression of HB-EGF. AU - Hollborn,Margrit, AU - Tenckhoff,Solveig, AU - Jahn,Karsten, AU - Iandiev,Ianors, AU - Biedermann,Bernd, AU - Schnurrbusch,Ute E K, AU - Limb,G Astrid, AU - Reichenbach,Andreas, AU - Wolf,Sebastian, AU - Wiedemann,Peter, AU - Kohen,Leon, AU - Bringmann,Andreas, Y1 - 2005/06/10/ PY - 2005/7/1/pubmed PY - 2006/4/14/medline PY - 2005/7/1/entrez SP - 397 EP - 413 JF - Molecular vision JO - Mol. Vis. VL - 11 N2 - PURPOSE: To compare the gene expression pattern of control postmortem retinas with retinas from patients with proliferative vitreoretinopathy (PVR), to determine the expression of the heparin binding epidermal growth factor-like growth factor (HB-EGF) by glial cells in fibroproliferative membranes, and to examine whether cells of the human Müller cell line, MIO-M1, respond to HB-EGF with proliferation, migration, and secretion of the vascular endothelial growth factor (VEGF). METHODS: To identify genes that were differently expressed in PVR and control retinas, the RNA from the neural retinas of seven postmortem donors and of two patients with PVR were analyzed for differential gene expression, by hybridization of labeled cRNA probes to an Affymetrix human genome microarray set. The results were validated by real time PCR experiments investigating RNA from 6 postmortem retinas and 4 PVR retinas. Epiretinal PVR membranes were immunohistochemically stained for colocalization of HB-EGF and the glial cell marker, glial fibrillary acidic protein (GFAP). The HB-EGF evoked proliferation of cultured Müller cells was investigated by a bromodeoxyuridine immunoassay, chemotaxis was assessed with a migration assay, and the release of VEGF was evaluated by ELISA. RESULTS: Out of the 12,600 genes and expressed sequence tags investigated, the levels of 80 showed an increased expression, and 21 were expressed at decreased levels, in the retinas of PVR patients compared to the control retinas. The upregulated signals include genes for nuclear and cell cycle related proteins, extracellular secretory proteins, cytosolic signaling proteins, and proteins of the membrane and the extracellular matrix. The genes of the hepatocyte growth factor and of HB-EGF were found to be expressed in PVR retinas but not in control retinas. In epiretinal membranes of patients with PVR, HB-EGF immunoreactivity partially colocalized with GFAP. In cultured Müller cells, HB-EGF stimulated both proliferation and chemotaxis, and the secretion of VEGF, via activation of the extracellular signal regulated kinases 1 and 2 and of the phosphatidylinositol-3 kinase. CONCLUSIONS: The development of PVR is accompanied by complex changes of the gene expression in the neural retina, with an upregulation of genes that support cell proliferation, cell signaling, cell motility, and extracellular matrix remodeling. HB-EGF is one of the factors that are significantly upregulated in PVR retinas. HB-EGF expression in fibroproliferative tissue and its stimulatory effect on glial cell proliferation, chemotaxis, and VEGF secretion suggest that HB-EGF may be a factor mediating glial cell responses during PVR. SN - 1090-0535 UR - https://www.unboundmedicine.com/medline/citation/15988409/Changes_in_retinal_gene_expression_in_proliferative_vitreoretinopathy:_glial_cell_expression_of_HB_EGF_ L2 - http://www.molvis.org/molvis/v11/a47/ DB - PRIME DP - Unbound Medicine ER -