July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Differential ECM Related Gene Expression in The Human Lamina Cribrosa in Populations at Increased Risk for Primary Open Angle Glaucoma
Author Affiliations & Notes
  • Amy Hill
    Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Jason Shoemaker
    Chemical and Petroleum Engineering, University of Pittsburgh, Pittsuburgh, Pennsylvania, United States
  • Catalina Ardila
    Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Jonathan Pieter Vande Geest
    Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Amy Hill, None; Jason Shoemaker, None; Catalina Ardila, None; Jonathan Vande Geest, None
  • Footnotes
    Support  NIH 2015 R01 EY
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3527. doi:
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      Amy Hill, Jason Shoemaker, Catalina Ardila, Jonathan Pieter Vande Geest; Differential ECM Related Gene Expression in The Human Lamina Cribrosa in Populations at Increased Risk for Primary Open Angle Glaucoma. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3527.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Glaucoma is expected to affect nearly 80 million people by the year 2020. Glaucomatous optic neuropathy is characterized by a loss of retinal ganglion cells at the site of the Lamina Cribrosa (LC). Experiments have shown that astrocytes are one of the most prevalent cell types in the LC and have been found to play an important role in the ECM remodeling of the LC that occurs in glaucoma. Those of African descent (AD) and Hispanic Ethnicity (HE) are at a greater risk for primary open angle glaucoma (POAG) than those of European descent (ED). The purpose of this experiment was to identify the differential gene expression of astrocytes seeded on decellularized human LCs from various racioethnicities.

Methods : Decellularized human posterior poles of African descent, European descent, and Hispanic Ethnicity (n=3) were seeded with human astrocytes and cultured for seven days. The LCs were isolated with a 3mm biopsy punch and immediately snap frozen in liquid nitrogen. Gene expression was quantified using an Affymetrix Clariom S Array. Microarray data was fit to a linear model, using LIMMA and the Benjamin-Hochberg method was used on the resulting p-values to control false discovery rate (FDR). For this preliminary study an FDR of 0.1 was required for a gene to be considered differentially expressed.

Results : The majority of the differentially expressed genes were recognized as glycoproteins. Two of the more interesting proteins, GREMLIN and plasminogen (PLG), were disproportionately regulated in astrocytes seeded on AD and HIS versus ED LCs.

Conclusions : GREMLIN is known to act as an antagonist for BMP-4, a natural inhibitor of the TGFβ2 pathway - which is known to mediate ECM synthesis and remodeling. GREMLIN has also been found to be upregulated in the region of the LC in glaucomatous tissues. The data in this experiment suggests that TGFβ2 activity may be increased in the AD LCs due to dysregulation of GREMLIN gene expression. We also found that PLG, which binds directly to the ECM and regulates proteolysis, is altered in astrocytes seeded on HE LCs. Our data suggests that those at higher risk for POAG may have varying changes in the ECM due to dysregulation of GREMLIN and PLG.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Figure 1. Heatmap of microarray differential expression for astrocytes seeded on decellularized AD, HE, and ED LCs. The arrows indicate genes of interest.

Figure 1. Heatmap of microarray differential expression for astrocytes seeded on decellularized AD, HE, and ED LCs. The arrows indicate genes of interest.

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