• apoptosis
• glaucoma
• neurodegeneration

• PCR, polymerase chain reaction
• POAG, primary open angle glaucoma

Primary open angle glaucoma (POAG) is the second commonest cause of blind registration in the United Kingdom and affects approximately 70 million people worldwide.^1,2 The major risk factors are intraocular pressure, ethnicity, refractive errors, and vascular function. There is also clear evidence from population, case control, and twin studies of a heritable element to POAG.^3,4 The genes encoding myocilin and optineurin have been be linked to POAG in large families with autosomal dominant inheritance, and a number of chromosomal loci are being studied for a possible genetic association with glaucoma.^5–10 It appears that POAG is a complex trait and multiple genes contribute to the phenotype and increase individuals’ susceptibility to glaucomatous optic neuropathy.

Quite independently, a number of recent studies suggest that apoptosis of the retinal ganglion cells is an important mechanism behind glaucoma.^11,12 Apoptosis is a form of genetically controlled, programmed cell death, which is under extensive research, especially in cancer,^13–15 neuronal injury,¹⁶ and neurodegenerative disorders.^17,18 During the primary regulatory steps of apoptosis, a signal of cellular distress activates the tumour suppressor protein p53. This protein acts like a “guardian of the genome”, regulating subsequent apoptotic events through several oncogenes, principally bax and bcl-2.¹³ Further apoptotic events include changes in mitochondria with cytochrome c release and activation of cystein proteases (caspases), which digest the dying cell from within.¹⁹

It is therefore of great interest that one study showed an association between genetic polymorphic variants of the p53 gene and POAG. In a Chinese study, a cytosine (C) residue at codon 72 of the p53 gene was significantly more common in POAG patients than control subjects.²⁰ In another study carried out on an Indian cohort, a second polymorphism (a 16 bp duplication in …