8-OHdG is one of the most abundant forms of oxidative damage products of DNA.
28 The modified DNA is excised and exported into serum, urine, or other extracellular fluids without further metabolism.
29 –31 Excretion of 8-OHdG into urine represents the average rate of oxidative damage in the whole body.
32 The 8-OHdG level in the extracellular fluid that is isolated from the systemic circulation, such as cerebrospinal fluid (CSF) and aqueous humor, may reflect oxidative damage of the organ.
33 –35 The 8-OHdG level in the CSF of patients with neurodegenerative diseases was significantly higher than in the CSF of control patients,
34,36 and the level was positively correlated with the duration of illness.
35,37 Aqueous humor is an intraocular fluid isolated from the systemic circulation (blood-aqueous barrier); its 8-OHdG content may reflect intraocular oxidative damage status. Moreover, the 8-OHdG concentration in the aqueous humor was positively correlated with the area of macular lesion that represented the area of retinal damage. We are unable to postulate at this stage whether the increased 8-OHdG concentration in aqueous humor is a primary event or is secondary to CNV growth. In vitro study found that oxidative stress on RPE can upregulate the secretion of vascular endothelial growth factor (VEGF),
38 which is a potent stimulator of neovascularization. Several transcription factors that enhance expression of VEGF are also regulated by reactive oxygen species.
39,40 Animal studies found more severe neovascularization growth in the mice deficient in superoxide dismutase 1 (
Sod1 −/−), which had increased constitutive and stimulated oxidative damage in the retina,
41 compared with that in the
Sod1 +/+ mice under the stimulation of VEGF.
42 On the other hand, retinal neovascularization may also cause retinal oxidative damage. Animal studies of the
Vldlr −/− mice, which had a defective gene for VLDL receptor and developed aberrant subretinal neovascularization, showed increased oxidative stress and neuronal degeneration limited to the region with neovascularization even in the absence of clinically significant leakage or hemorrhage, and the degeneration was attenuated significantly by antioxidants.
43 Further studies to analyze the oxidative stress level in patients with extensive early stage AMD without CNV growth may help to delineate this issue.