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Bioinformatic and statistical analysis of the optic nerve head in a primate model of ocular hypertension.

Kompass KS, Agapova OA, Li W, Kaufman PL, Rasmussen CA, Hernandez MR - BMC Neurosci (2008)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St, Louis, MO 63110, USA. kompass@vision.wustl.edu

ABSTRACT

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.

Conclusion: 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.

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Related in: MedlinePlus

Intraocular pressure measurements for five paired glaucomatous samples. Intraocular pressure measurements from day of first laser in ExpG eye to sacrifice. Day 0 (vertical line) is the first time intraocular pressure was above 25 mm Hg.
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Figure 1: Intraocular pressure measurements for five paired glaucomatous samples. Intraocular pressure measurements from day of first laser in ExpG eye to sacrifice. Day 0 (vertical line) is the first time intraocular pressure was above 25 mm Hg.

Mentions: Intraocular pressure readings from Goldmann applanation tonometry are shown in Figure 1 from the first reading above 25 mm Hg in each laser treated eye. Table 1 and Table 2 show physiological data for all samples processed for microarray.


Bioinformatic and statistical analysis of the optic nerve head in a primate model of ocular hypertension.

Kompass KS, Agapova OA, Li W, Kaufman PL, Rasmussen CA, Hernandez MR - BMC Neurosci (2008)

Intraocular pressure measurements for five paired glaucomatous samples. Intraocular pressure measurements from day of first laser in ExpG eye to sacrifice. Day 0 (vertical line) is the first time intraocular pressure was above 25 mm Hg.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2567987&req=5

Figure 1: Intraocular pressure measurements for five paired glaucomatous samples. Intraocular pressure measurements from day of first laser in ExpG eye to sacrifice. Day 0 (vertical line) is the first time intraocular pressure was above 25 mm Hg.
Mentions: Intraocular pressure readings from Goldmann applanation tonometry are shown in Figure 1 from the first reading above 25 mm Hg in each laser treated eye. Table 1 and Table 2 show physiological data for all samples processed for microarray.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St, Louis, MO 63110, USA. kompass@vision.wustl.edu

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus