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Ocular expression and distribution of products of the POAG-Associated chromosome 9p21 Gene Region

Citation

Chidlow, G and Wood, JPM and Sharma, S and Dimasi, DP and Burdon, KP and Casson, RJ and Craig, JE, Ocular expression and distribution of products of the POAG-Associated chromosome 9p21 Gene Region, PL o S One, 8, (9) Article e75067. ISSN 1932-6203 (2013) [Refereed Article]


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Copyright 2013 the Authors.

DOI: doi:10.1371/journal.pone.0075067

Abstract

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-5′-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.

Item Details

Item Type:Refereed Article
Keywords:cyclin dependent kinase inhibitor 2A; cyclin dependent kinase inhibitor 2B; messenger RNA; methyl 5' thioadenosine phosphorylase; peptides and proteins; protein p164ARF; unclassified drug
Research Division:Medical and Health Sciences
Research Group:Ophthalmology and Optometry
Research Field:Vision Science
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Hearing, Vision, Speech and Their Disorders
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
ID Code:90064
Year Published:2013
Web of Science® Times Cited:7
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-03-26
Last Modified:2014-04-30
Downloads:437 View Download Statistics

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