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Editors Selection IGR 8-4

Surgical management of glaucoma

Comment by Mark Sherwood on:

11817 Adenoviral p53 gene transfer inhibits human Tenon's capsule fibroblast proliferation, Johnson KT; Rodicker F; Heise K et al., British Journal of Ophthalmology, 2005; 89: 508-512

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New, more selective, agents to decrease wound healing following glaucoma surgery have been sought in recent years to replace antiproliferative agents such as 5-fluorouracil and mitomycin-c, due to their associated increased long-term complications including bleb leak, hypotony and endophthalmitis. A human monoclonal antibody to TGF-β 2 has been clinically investigated but recent phase III study results have so far failed to confirm adequate efficacy. A single application of b-irradiation has been shown to lead to growth arrest in human Tenons fibroblasts but, although this irradiation has been demonstrated to be helpful in improving the success rate of bleb survival, it has not achieved common clinical usage. Constable et al. (1998) found that b-irradiation increased expression of the tumour suppressor gene p53 in human Tenons fibroblast cells and El-Diery and co-workers have suggested that the p53 mediated G1 arrest requires p21^WAF-1/Cip1. Viral gene transfer of this p21^WAF-1/Cip1 has been shown to improve filtration surgery survival in both a rabbit and primate model. Johnson et al. (351), using a recombinant adenoviral vector to deliver transgenes encoding for human p53, were able to produce an overexpression of p53 in human Tenons fibroblast cells in culture. With several techniques they were able to confirm that infection with rAd.p53 produced a significant inhibition of cell proliferation, DNA synthesis and metabolic activity in vitro, without increasing apoptosis. They also showed that p53 induces an increase in p21^WAF-1/Cip1 confirming this important downstream pathway. Their study is important in highlighting that p53 gene upregulation may decrease scarring following glaucoma surgery by utilizing the cell cycle pathways to selectively and reversibly inhibit cell proliferation while avoiding apoptotic cell death and hypocellularity, which can enhance risks of late complications

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