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Gerassimos Lascaratos, David Chau, Haogang Zhu, Anthony Schapira, David Garway-Heath; Mitochondrial membrane potential, as a measure of mitochondrial function, in patients with normal tension glaucoma vs ocular hypertension. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1604.
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© ARVO (1962-2015); The Authors (2016-present)
The mitochondrial membrane potential (ΔΨm) is a key indicator of mitochondrial function and the characterization of ΔΨm in situ allows for an accurate determination of mitochondrial bioenergetics. To explore the role of systemic mitochondrial function in glaucoma, we measured the ΔΨm in the lymphocytes of healthy subjects and patients, contrasting individuals at the extremes of intraocular pressure (IOP) susceptibility - rapidly progressing patients with Normal Tension Glaucoma (NTG) and non-progressing with Ocular Hypertension (OHT).
Two cohorts of 30 subjects with ≥8 Humphrey 24-2 visual fields over ≥5 years of follow-up were recruited prospectively from Moorfields Eye Hospital: a) NTG patients with Mean Deviation change > -1.0 dB/yr and mean IOP<16; b) non-progressing OHT 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 and maintained under unstimulated conditions. Rotenone(0.5µM 24hrs), a complex I inhibitor, was added to assess the susceptibility of lymphocytes to an insult causing mitochondrial dysfunction. Cells were stained with the fluorescent red dye TMRM(25nM), incubated at room temperature for 30min and analysed by flow cytometry(FACS Calibur, CellQuest software). A human lymphocytic cell line(Raji) served as internal control across experiments. Wilcoxon signed rank test was used to compare groups(SPSS 20).
The TMRM staining expressed as the mean red fluorescence % difference from Raji (mean±SD) for the control, NTG and OHT groups was 168.5±39.9, 166.2±39.2 and 187.2±46.2, respectively. The OHT lymphocyte ΔΨm was significantly higher than that in the NTG (p<0.01) and control (p<0.05) groups. Upon rotenone treatment, the TMRM staining for the control, NTG and OHT groups was reduced to 140.5±31.8 (p<0.001 compared to baseline), 141.4±36.6 (p<0.001) and 157.1±41.7 (p<0.001), respectively.
Our data suggest, for the first time, that OHT patients may have healthier mitochondria at a systemic level, when compared to NTG patients and controls. This study implicates the role of healthy systemic mitochondria in resistance to glaucomatous optic neuropathy development and progression, particularly in the context of OHT.
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