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Bledi Petriti, David Chau, Gerassimos Lascaratos, Philip Campbell, Georgios Lazaridis, David F Garway-Heath; Normal Tension Glaucoma patients have reduced systemic mitochondrial function compared to High Tension Glaucoma patients. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1009.
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While raised intraocular pressure (IOP) is the main risk factor for primary open angle glaucoma progression, patients deteriorate at all levels of IOP and despite eye pressure lowering. In Normal tension glaucoma (NTG) vision loss occurs with IOP within the normal healthy population range, suggesting other factors confer susceptibility. Growing evidence suggests mitochondrial dysfunction contributes to an increasing number of ageing-associated neurodegenerative diseases including glaucoma. Given the high energy requirements of the unmyelinated retinal ganglion cell axons and optic nerve head astrocytes, mitochondrial function is a candidate susceptibility factor. We want to identify whether there is a subset of glaucoma patients with mitochondrial dysfunction who may be suitable for personalised (stratified) therapeutic intervention. We hypothesise such patients will be mostly found amongst the NTG cohort compared to the High tension glaucoma (HTG) cohort
Mitochondrial function was measured in lymphocytes using the XFe24 Analyzer on 57 HTG and 84 NTG white-European, age similar patients. Inclusion criteria: minimum 5 years follow up with at least 8 reliable visual fields and absence of: a cause of secondary and narrow angle glaucoma, active haematological malignancy, recent infection/chemotherapy/radiotherapy and drugs known to affect mitochondrial function. Sequential addition of ATP synthase inhibitor oligomycin, FCCP (protonophoric uncoupler), and electron transport inhibitors rotenone/antimycin A, enabled measurement of various parameters of mitochondria function
Mean (SD) Basal Respiration, Maximal Respiration, Spare Respiratory Capacity and ATP production (all pmol/min) were significantly lower (p<0.001) in the NTG group: 154.6 (42.1), 999.2 (300.6) 844.6 (271.4) and 139.3 (37.2), compared to the HTG group: 182.5 (32.9), 1181.5 (254), 999.0 (234.3) and 164.6 (26.0) respectively, (Figure). Proton leak (pmol/min) was not significantly different (p=0.1) between the NTG and HTG cohorts: 16.1 (8.6) and 19.1 (11.6), respectively
Our data show strong evidence of a reduction of various components of systemic (lymphocyte) mitochondrial function in the NTG, compared to the HTG cohort, supporting mitochondrial function as a glaucoma susceptibility factor and potential therapeutic target.
This is a 2020 ARVO Annual Meeting abstract.
Mitochondrial function parameters in the NTG and HTG cohorts
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