Differential global and extra-cellular matrix focused gene expression patterns between normal and glaucomatous human...

Area of Science:

• Ophthalmology
• Cell Biology
• Genomics

Background:

• Primary open-angle glaucoma (POAG) is characterized by significant extracellular matrix (ECM) remodeling in the optic nerve head.
• Glial fibrillary acid protein (GFAP)-negative lamina cribrosa (LC) cells are implicated in this remodeling process.

Purpose of the Study:

• To investigate global and ECM-focused gene transcription differences between GFAP-negative LC cells from normal and POAG human donors.
• To identify potential molecular mechanisms underlying optic nerve head changes in POAG.

Main Methods:

• Generation of GFAP-negative LC cell lines from normal (n=4) and POAG (n=4) human donors.
• Comparison of transcriptional profiles using Affymetrix U133A arrays.
• Validation of microarray data via real-time TaqMan PCR and immunohistochemistry.

Main Results:

• 183 genes were upregulated and 220 downregulated (>1.5 fold) in POAG LC cells compared to controls.
• Key upregulated genes include TGFbeta1, SPARC, POSTN, THBS1, and collagens (COL1A1, COL5A1, COL11A1).
• ECM genes were identified as a statistically over-represented class in POAG LC cells.

Conclusions:

• POAG LC cells exhibit upregulated ECM and pro-fibrotic gene expression in vitro.
• This altered gene expression may be a pathological feature of LC cells in POAG in vivo.
• LC cells could be key regulators of optic nerve head ECM remodeling and potential therapeutic targets.