June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Reduced Expression of the Cell Cycle Inhibitors p27 and p57 and Increased Proliferation in Glaucoma Lamina Cribrosa Cells
Author Affiliations & Notes
  • Colm J O'Brien
    Ophthalmology, Mater Misericordiae Univ Hospital, Dublin, Ireland
  • Sara McNally
    Ophthalmology, Mater Misericordiae Univ Hospital, Dublin, Ireland
  • Ruaidhri Kirwan
    School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
  • Abbot F Clark
    U. North Texas Health Science Center, Forth Worth, TX
  • Deborah Wallace
    Ophthalmology, Mater Misericordiae Univ Hospital, Dublin, Ireland
    School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
  • Footnotes
    Commercial Relationships Colm O'Brien, None; Sara McNally, None; Ruaidhri Kirwan, None; Abbot Clark, None; Deborah Wallace, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3675. doi:
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      Colm J O'Brien, Sara McNally, Ruaidhri Kirwan, Abbot F Clark, Deborah Wallace; Reduced Expression of the Cell Cycle Inhibitors p27 and p57 and Increased Proliferation in Glaucoma Lamina Cribrosa Cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3675.

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

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Abstract

Purpose: Recent GWAS studies show that SNPs in the cell cycle gene CDKN2B-AS are associated with an increased vertical cup to disc ratio in glaucoma. Here we explore cell cycle gene expression and cell proliferation in glaucoma lamina cribrosa (LC) cells.

Methods: We used human donor LC cells (normal and glaucoma) and used Affymetrix Chip microarray technology to study differential gene expression and performed optic nerve head immuno-histochemistry (IHC) with p27(Kip1) and p57(Kip2) antibodies from Leica. Cell proliferation was studied using the MTS assay.

Results: The gene chip data showed a significant signal log ratio (SLR) down-regulation in p27(-0.6) and p57(-0.9) in the glaucoma LC cells and the IHC confirmed the reduced p27 and p57 expression in ONH in glaucoma. After 48 hours in routine culture on non-coated tissue culture plastic, glaucoma LC cells show higher proliferation indices than normal control cells. TGF-b treatment of normal LC cells also reduced the SLR in p27(-0.6) and p57(-0.7).

Conclusions: This study demonstrates increased proliferation in glaucoma LC cells associated with reduced expression of the cell cycle inhibitors p27/p57, which may help to explain the activated myofibroblast nature of LC cells in glaucoma.

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