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PMID: 20847120 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Cell proliferation and interleukin-6-type cytokine signaling are implicated by gene expression responses in early optic nerve head injury in rat glaucoma.

Investigative ophthalmology & visual science ·Vol. 52 ·No. 1 ·2011-01-00 ·Pages 504-18

Johnson EC, Doser TA, Cepurna WO, Dyck JA, Jia L, Guo Y, Lambert WS, Morrison JC

Abstract

In glaucoma, the optic nerve head (ONH) is the principal site of initial axonal injury, and elevated intraocular pressure (IOP) is the predominant risk factor. However, the initial responses of the ONH to elevated IOP are unknown. Here the authors use a rat glaucoma model to characterize ONH gene expression changes associated with early optic nerve injury. Unilateral IOP elevation was produced in rats by episcleral vein injection of hypertonic saline. ONH mRNA was extracted, and retrobulbar optic nerve cross-sections were graded for axonal degeneration. Gene expression was determined by microarray and quantitative PCR (QPCR) analysis. Significantly altered gene expression was determined by multiclass analysis and ANOVA. DAVID gene ontology determined the functional categories of significantly affected genes. The Early Injury group consisted of ONH from eyes with <15% axon degeneration. By array analysis, 877 genes were significantly regulated in this group. The most significant upregulated gene categories were cell cycle, cytoskeleton, and immune system process, whereas the downregulated categories included glucose and lipid metabolism. QPCR confirmed the upregulation of cell cycle-associated genes and leukemia inhibitory factor (Lif) and revealed alterations in expression of other IL-6-type cytokines and Jak-Stat signaling pathway components, including increased expression of IL-6 (1553%). In contrast, astrocytic glial fibrillary acidic protein (Gfap) message levels were unaltered, and other astrocytic markers were significantly downregulated. Microglial activation and vascular-associated gene responses were identified. Cell proliferation and IL-6-type cytokine gene expression, rather than astrocyte hypertrophy, characterize early pressure-induced ONH injury.

MeSH Terms
Animals Axons/metabolism,pathology Cell Proliferation Disease Models, Animal Gene Expression Regulation/physiology Glaucoma/genetics,pathology Interleukin-6/genetics Intraocular Pressure Male Microarray Analysis Nerve Degeneration/genetics,pathology Optic Disk/metabolism,pathology Optic Nerve Injuries/genetics,pathology Polymerase Chain Reaction RNA, Messenger/genetics Rats Rats, Inbred BN Signal Transduction/physiology
Chemicals
Interleukin-6 RNA, Messenger
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Johnson Elaine C
Kenneth C. Swan Ocular Neurobiology Laboratory, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon 97201, USA. [email protected]
Doser Thomas A
Cepurna William O
Dyck Jennifer A
Jia Lijun
Guo Ying
Lambert Wendi S
Morrison John C
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Article Info
Journal
Investigative ophthalmology & visual science
Abbr.
Invest Ophthalmol Vis Sci
ISSN
1552-5783
DOI
10.1167/iovs.10-5317
Email
[email protected]
Published
2011-01-00
Epub
2011-00-25
Pages
504-18
Language
English
Region
United States
NLM ID
7703701
PMCID
PMC3053294
Subset
IM
Grants
NEI NIH HHS · R01 EY010145 · United States
NEI NIH HHS · R01 EY016866 · United States
NEI NIH HHS · EY010145 · United States
NEI NIH HHS · EY016866 · United States
External Links
PubMed source DOI: 10.1167/iovs.10-5317 PMC Full Text View journal details
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