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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)
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.
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.
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).
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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