Topical mitomycin C is widely used as a surgical adjuvant in
glaucoma filtration surgery
1 and is effective in the
treatment of pterygium, primary acquired melanosis, conjunctival
melanoma, ocular cicatricial pemphigoid, and corneal and conjunctival
epithelial dysplasia and neoplasia and in optic nerve decompression
surgery for pseudotumor cerebri.
2 3 4 5 6 7 8 9 10 11 It is under
investigation for the treatment of proliferative
vitreoretinopathy.
12 Complications associated with topical
ophthalmic mitomycin C therapy include corneal epitheliopathy, ulcers
and perforation, scleral melting, bleb leaks, hypotony,
endophthalmitis, and neuroretinitis.
13 14 15 16 17 Mitomycin C is
a bifunctional alkylating agent that must undergo bioreductive
activation to exert an antitumor effect.
18 NAD(P)H:quinone
oxidoreductase (EC 1.6.99.2, NQO1) or DT-diaphorase is a cytosolic
obligate two-electron reductase that can induce bioactivation of
mitomycin C in vitro and plays an important role in its bioactivation
in vivo.
18 19 20 21 Previous immunohistochemical studies have
localized NQO1 in human lung epithelial cancers and in normal
respiratory epithelium, vascular endothelium, and
adipocytes,
22 but to our knowledge there has been no
report describing the distribution of NQO1 in the human eye. In
addition, a polymorphism in NQO1 (NQO1*2) has been characterized
recently.
23 Among whites, the prevalence of the NQO1*2
polymorphism is approximately 4% to 7%, but it may be as high as 15%
to 20% in Hispanic and Asian populations.
23 24 Tissues
and cell lines derived from individuals homozygous for the NQO1*2
polymorphism have markedly reduced NQO1 activity and
protein.
25