Bioinformatic and statistical analysis of the optic nerve head in a primate model of ocular hypertension.
BACKGROUND
The nonhuman primate model of glaucomatous optic neuropathy most faithfully reproduces the human disease. We used high-density oligonucleotide arrays to investigate whole genome transcriptional changes occurring at the optic nerve head during primate experimental glaucoma.


RESULTS
Laser scarification of the trabecular meshwork of cynomolgus macaques produced elevated intraocular pressure that was monitored over time and led to varying degrees of damage in different samples. The macaques were examined clinically before enucleation and the myelinated optic nerves were processed post-mortem to determine the degree of neuronal loss. Global gene expression was examined in dissected optic nerve heads with Affymetrix GeneChip microarrays. We validated a subset of differentially expressed genes using qRT-PCR, immunohistochemistry, and immuno-enriched astrocytes from healthy and glaucomatous human donors. These genes have previously defined roles in axonal outgrowth, immune response, cell motility, neuroprotection, and extracellular matrix remodeling.


CONCLUSIONS
Our findings show that glaucoma is associated with increased expression of genes that mediate axonal outgrowth, immune response, cell motility, neuroprotection, and ECM remodeling. These studies also reveal that, as glaucoma progresses, retinal ganglion cell axons may make a regenerative attempt to restore lost nerve cell contact.
Kompass
Kenneth S
KS
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St, Louis, MO 63110, USA. kompass@vision.wustl.edu
Agapova
Olga A
OA
Li
Wenjun
W
Kaufman
Paul L
PL
Rasmussen
Carol A
CA
Hernandez
M Rosario
MR
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001369:Axons / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005123:Eye / Q000473:pathology; D058851:GPI-Linked Proteins; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D005901:Glaucoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007429:Intraocular Pressure / Q000502:physiology; D008252:Macaca fascicularis; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D009798:Ocular Hypertension / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000706:statistics & numerical data; D009898:Optic Disk / Q000378:metabolism / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050777:Stathmin / Q000235:genetics / Q000378:metabolism; D014129:Trabecular Meshwork / Q000473:pathology / Q000503:physiopathology
D058851:GPI-Linked Proteins; C503042:GPNMB protein, human; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; C484539:NRN1 protein, human; D009479:Neuropeptides; C493995:STMN1 protein, human; D050777:Stathmin