Ocular expression and distribution of products of the POAG-associated chromosome 9p21 gene region.
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/p15(INK4B) , CDKN2A/p16(INK4A) and p14ARF (rat equivalent, p19(ARF) ) 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 p16(INK4A) 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. P19(ARF) 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 P19(ARF)/p14(ARF) proteins in either rat or human eyes, respectively. In contrast, p15(INK4B) mRNA was detected in much higher amounts in both retina and optic nerve compared with the other genes under analysis. Moreover, p15(INK4B) 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.
Ophthalmic Research Laboratories, South Australian Institute of Ophthalmology, Hanson Institute Centre for Neurological Diseases, Adelaide, South Australia, Australia ; Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, South Australia, Australia.
Glyn
G
Chidlow
John P M
JP
Wood
Shiwani
S
Sharma
David P
DP
Dimasi
Kathryn P
KP
Burdon
Robert J
RJ
Casson
Jamie E
JE
Craig
D000368:Aged; D000818:Animals; D002460:Cell Line; D002899:Chromosomes, Human, Pair 9; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D023061:Gene Order; D056726:Genetic Association Studies; D056426:Genetic Loci; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D005810:Multigene Family; D009928:Organ Specificity / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger