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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.

Ocular Expression and Distribution of Products of the POAG-Associated Chromosome 9p21 Gene Region