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Expression of acute-phase response proteins in retinal Müller cells in diabetes.
Invest Ophthalmol Vis Sci. 2005 Jan; 46(1):349-57.IO

Abstract

PURPOSE

To characterize the whole spectrum of gene expression changes induced by diabetes in retinal Müller glial cells.

METHODS

Müller cells were isolated from the retina of streptozotocin-diabetic and age-matched control rats by gradient centrifugation and immediately processed for RNA isolation. The gene expression profile of Müller cells was studied with the GeneChip Rat Genome oligonucleotide array (Affymetrix, Santa Clara, CA). The upregulation of acute-phase proteins in the retina of diabetic rats was confirmed by Northern and Western blot analyses. Real-time-RT-PCR was used to study the retinal expression of inflammatory cytokines.

RESULTS

Gene expression profiling identified 78 genes as differentially expressed in diabetic Müller cells. One third of these genes were associated with inflammation, including a large cluster (18% of the differentially expressed genes) of acute-phase response proteins: alpha2-macroglobulin, ceruloplasmin, complement components, lipocalin-2, metallothionein, serine protease inhibitor-2, transferrin, tissue inhibitor of metalloproteases-1, transthyretin, and the transcription factor C/EBPdelta. Northern and Western blot analyses confirmed the upregulation of alpha2-macroglobulin and ceruloplasmin in the diabetic retina, but not in the cerebral cortex and liver of the same animals. The acute-phase response of Müller cells in diabetes was associated with upregulation of interleukin (IL)-1beta in the retina.

CONCLUSIONS

Müller cells acquire a complex and specific reactive phenotype in diabetes characterized by the induction of acute-phase response proteins and other inflammation-related genes. The concomitant upregulation of IL-1beta in the retina of diabetic rats points to this cytokine as a possible mediator of the acute-phase response mounted by Müller cells in diabetes.

Authors+Show Affiliations

Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA. chiara@vision.eri.harvard.eduNo 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

15623795

Citation

Gerhardinger, Chiara, et al. "Expression of Acute-phase Response Proteins in Retinal Müller Cells in Diabetes." Investigative Ophthalmology & Visual Science, vol. 46, no. 1, 2005, pp. 349-57.
Gerhardinger C, Costa MB, Coulombe MC, et al. Expression of acute-phase response proteins in retinal Müller cells in diabetes. Invest Ophthalmol Vis Sci. 2005;46(1):349-57.
Gerhardinger, C., Costa, M. B., Coulombe, M. C., Toth, I., Hoehn, T., & Grosu, P. (2005). Expression of acute-phase response proteins in retinal Müller cells in diabetes. Investigative Ophthalmology & Visual Science, 46(1), 349-57.
Gerhardinger C, et al. Expression of Acute-phase Response Proteins in Retinal Müller Cells in Diabetes. Invest Ophthalmol Vis Sci. 2005;46(1):349-57. PubMed PMID: 15623795.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of acute-phase response proteins in retinal Müller cells in diabetes. AU - Gerhardinger,Chiara, AU - Costa,Montserrat Biarnés, AU - Coulombe,Mary C, AU - Toth,Ildiko, AU - Hoehn,Todd, AU - Grosu,Paul, PY - 2004/12/30/pubmed PY - 2005/2/11/medline PY - 2004/12/30/entrez SP - 349 EP - 57 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 46 IS - 1 N2 - PURPOSE: To characterize the whole spectrum of gene expression changes induced by diabetes in retinal Müller glial cells. METHODS: Müller cells were isolated from the retina of streptozotocin-diabetic and age-matched control rats by gradient centrifugation and immediately processed for RNA isolation. The gene expression profile of Müller cells was studied with the GeneChip Rat Genome oligonucleotide array (Affymetrix, Santa Clara, CA). The upregulation of acute-phase proteins in the retina of diabetic rats was confirmed by Northern and Western blot analyses. Real-time-RT-PCR was used to study the retinal expression of inflammatory cytokines. RESULTS: Gene expression profiling identified 78 genes as differentially expressed in diabetic Müller cells. One third of these genes were associated with inflammation, including a large cluster (18% of the differentially expressed genes) of acute-phase response proteins: alpha2-macroglobulin, ceruloplasmin, complement components, lipocalin-2, metallothionein, serine protease inhibitor-2, transferrin, tissue inhibitor of metalloproteases-1, transthyretin, and the transcription factor C/EBPdelta. Northern and Western blot analyses confirmed the upregulation of alpha2-macroglobulin and ceruloplasmin in the diabetic retina, but not in the cerebral cortex and liver of the same animals. The acute-phase response of Müller cells in diabetes was associated with upregulation of interleukin (IL)-1beta in the retina. CONCLUSIONS: Müller cells acquire a complex and specific reactive phenotype in diabetes characterized by the induction of acute-phase response proteins and other inflammation-related genes. The concomitant upregulation of IL-1beta in the retina of diabetic rats points to this cytokine as a possible mediator of the acute-phase response mounted by Müller cells in diabetes. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/15623795/Expression_of_acute_phase_response_proteins_in_retinal_Müller_cells_in_diabetes_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.04-0860 DB - PRIME DP - Unbound Medicine ER -