Ocular Expression and Distribution of Products of the POAG-Associated Chromosome 9p21 Gene Region
View/ Open
Date
2013-09Author
Chidlow, Glyn
Wood, John P M
Sharma, Shiwani
Dimasi, David Paul
Burdon, Kathryn Penelope
Casson, Robert J
Craig, Jamie E
Metadata
Show full item recordAbstract
It has recently been shown that there are highly significant associations for common single nucleotide polymorphisms
(SNPs) near the CDKN2B-AS1 gene region at the 9p21 locus with primary open angle glaucoma (POAG), a leading cause of
irreversible blindness. This gene region houses the CDKN2B/p15INK4B
, CDKN2A/p16INK4A and p14ARF (rat equivalent, p19ARF)
tumour suppressor genes and is adjacent to the S-methyl-59-thioadenosine phosphorylase (MTAP) gene. In order to
understand the ocular function of these genes and, therefore, how they may be involved in the pathogenesis of POAG, we
studied the distribution patterns of each of their products within human and rat ocular tissues. MTAP mRNA was detected in
the rat retina and optic nerve and its protein product was localised to the corneal epithelium, trabecular meshwork and
retinal glial cells in both human and rat eyes. There was a very low level of p16INK4A mRNA present within the rat retina and
slightly more in the optic nerve, although no protein product could be detected in either rat or human eyes with any of the
antibodies tested. P19ARF mRNA was likewise only present at very low levels in rat retina and slightly higher levels in the
optic nerve. However, no unambiguous evidence was found to indicate expression of specific P19ARF/p14ARF proteins in
either rat or human eyes, respectively. In contrast, p15INK4B mRNA was detected in much higher amounts in both retina and
optic nerve compared with the other genes under analysis. Moreover, p15INK4B protein was clearly localised to the retinal
inner nuclear and ganglion cell layers and the corneal epithelium and trabecular meshwork in rat and human eyes. The
presented data provide the basis for future studies that can explore the roles that these gene products may play in the
pathogenesis of glaucoma and other models of optic nerve damage.
Description
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.