Early gene expression changes in the retinal ganglion cell layer of a rat glaucoma model

Ying Guo, Elaine Johnson, William O. Cepurna, Jennifer A. Dyck, Tom Doser, John Morrison

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

PURPOSE. To identify patterns of early gene expression changes in the retinal ganglion cell layer (GCL) of a rodent model of chronic glaucoma. METHODS. Prolonged elevation of intraocular pressure (IOP) was produced in rats by episcleral vein injection of hypertonic saline (N = 30). GCLs isolated by laser capture microdissection were grouped by grading of the nerve injury (25% for advanced injury). Gene expression was determined by cDNA microarray of independent GCL RNA samples. Quantitative PCR (qPCR) was used to further examine the expression of selected genes. RESULTS. By array analysis, 533 GCL genes (225 up,308 down) were significantly regulated in early injury. Compared to only one major upregulated gene class of metabolism regulation, more were downregulated, including mitochondria, ribosome, proteasome, energy pathways, protein synthesis, protein folding, and synaptic transmission. qPCR confirmed an early upregulation of Atf3. With advanced injury, 1790 GCL genes were significantly regulated (997 up, 793 down). Altered gene categories included upregulated protein synthesis, immune response, and cell apoptosis and downregulated dendrite morphogenesis and axon extension. Of all the early changed genes, 50% were not present in advanced injury. These uniquely affected genes were mainly associated with upregulated transcription regulation and downregulated protein synthesis. CONCLUSIONS. Early GCL gene responses to pressure-induced injury are characterized by an upregulation of Atf3 and extensive downregulation in genes associated with cellular metabolism and neuronal functions. Most likely, these changes represent those specific to RGCs and are thus potentially important for enhancing RGC survival in glaucoma.

Original languageEnglish (US)
Pages (from-to)1460-1473
Number of pages14
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number3
DOIs
StatePublished - Mar 2011

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Retinal Ganglion Cells
Glaucoma
Gene Expression
Ganglia
Genes
Wounds and Injuries
Down-Regulation
Up-Regulation
Laser Capture Microdissection
Polymerase Chain Reaction
Proteins
Protein Folding
Proteasome Endopeptidase Complex
Dendrites
Oligonucleotide Array Sequence Analysis
Intraocular Pressure
Ribosomes
Morphogenesis
Synaptic Transmission
Axons

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Early gene expression changes in the retinal ganglion cell layer of a rat glaucoma model. / Guo, Ying; Johnson, Elaine; Cepurna, William O.; Dyck, Jennifer A.; Doser, Tom; Morrison, John.

In: Investigative Ophthalmology and Visual Science, Vol. 52, No. 3, 03.2011, p. 1460-1473.

Research output: Contribution to journalArticle

Guo, Ying ; Johnson, Elaine ; Cepurna, William O. ; Dyck, Jennifer A. ; Doser, Tom ; Morrison, John. / Early gene expression changes in the retinal ganglion cell layer of a rat glaucoma model. In: Investigative Ophthalmology and Visual Science. 2011 ; Vol. 52, No. 3. pp. 1460-1473.
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