Early gene expression changes in the retinal ganglion cell layer of a rat glaucoma model.
OBJECTIVE
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% axon degeneration for early 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.
Kenneth C. Swan Ocular Neurobiology Laboratory, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.
Ying
Y
Guo
Elaine C
EC
Johnson
William O
WO
Cepurna
Jennifer A
JA
Dyck
Tom
T
Doser
John C
JC
Morrison
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D005901:Glaucoma / Q000235:genetics*; D007429:Intraocular Pressure; D020411:Oligonucleotide Array Sequence Analysis; D020221:Optic Nerve Injuries / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005136:Eye Proteins