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Gerassimos Lascaratos, David Chau, Anthony H. Schapira, David F. Garway-Heath; Aconitase Activity, As A Measure Of Oxidative Stress, In Patients With Normal Tension Glaucoma Vs Ocular Hypertension - Preliminary Findings. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3843.
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© ARVO (1962-2015); The Authors (2016-present)
Aconitase, an iron-sulfur protein that catalyzes the stereospecific isomerization of citrate to isocitrate in the mitochondrial tricarboxylic acid cycle, is vulnerable to oxidative damage and has been widely used as a biochemical marker of cellular oxidative stress. In order to explore the role of systemic oxidative stress in glaucoma, we measured the aconitase activity in the lymphocytes of patients with and without exogenous oxidative stress induction, contrasting individuals at the extremes of intraocular pressure (IOP) susceptibility.
Two cohorts of 6 subjects with ≥8 Humphrey 24-2 visual fields over ≥5 years of follow-up were recruited prospectively from Moorfields Eye Hospital: a) Normal Tension Glaucoma (NTG) group: rapidly progressing patients with Mean Deviation change > -1.0 dB/yr and mean IOP<16; b) Ocular Hypertension (OHT) group: non-progressing patients with mean IOP>24. An equal number of age-similar subjects with normal IOP, healthy discs and no family history of glaucoma was recruited as controls. Lymphocytes were isolated, after the removal of monocytes, from anticoagulated peripheral blood using Lymphoprep, and maintained under unstimulated conditions. Paraquat (PQ), a potent free radical generator, was added (final concentration 100µM for 24hrs) to measure the susceptibility of lymphocytes to oxidative stress. Aconitase activity was measured by absorbance kinetics at 37°C after correction for protein level. Student’s t-test was used for the statistical analysis.
There were no statistically significant differences (mean±SEM) in baseline aconitase activity for the control, NTG and OHT groups: 1.23±0.11, 1.50±0.18 and 1.41±0.16 pmol/min/mg, respectively. Upon PQ treatment, the aconitase activity for the control, NTG and OHT groups was reduced to 82±4% (p<0.05 comparing to baseline), 79±6% (p<0.05) and 89±17% (p=0.46, not significant), respectively. Thus, a tentative finding, given the small number of subjects to date, is that OHT lymphocytes may be more resistant to the oxidative stress insult produced by PQ, comparing to the NTG and control groups.
Our preliminary data suggest, for the first time, that OHT patients may demonstrate an enhanced capacity to deal with oxidative stress at a systemic level, when compared to NTG patients and controls. This study implicates the role of systemic antioxidant capacity in resistance to glaucoma damage and glaucoma progression, particularly in the context of OHT.
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