Mitochondrial respiratory function is strongly associated with progressive glaucomatous vision loss

Abstract

Abstract Intraocular pressure (IOP) has been the only modifiable risk factor for glaucoma. However, glaucoma develops with high IOP (high tension glaucoma; HTG) and normal IOP (normal tension glaucoma; NTG) and many lose vision despite IOP-lowering treatment, suggesting other factors confer susceptibility. We demonstrate that lymphocyte/monocyte mitochondrial oxygen consumption rate (OCR) is lower in glaucoma patients than in controls (P < 0.001), is lower in NTG than HTG (P < 0.01) and lower OCR is strongly associated with faster visual field (VF) progression in patients treated by lowering IOP (P < 0.001), explaining 13% of variance in the rate of progression. In a reference cohort of untreated glaucoma patents, IOP explained 16% of VF progression variance. Lymphocyte/monocyte nicotinamide adenine dinucleotide (NAD) levels are lower in glaucoma patients (P < 0.001) and strongly associated with OCR (P < 0.001). Our results support mitochondrial OCR and NAD levels as new biomarkers for glaucoma progression susceptibility and new targets for treatment.