Abstract
Purpose :
Ocular hypertension (OHT) patients who are resistant to glaucomatous damage, have been shown to have better mitochondrial function in their peripheral blood lymphocytes and fibroblasts compared to age-matched controls. Similarly patients with normal tension glaucoma have been shown to have poorer mitochondrial function in fibroblasts than age-matched controls. We aim to use mitochondrial function as a therapeutic target for the treatment of glaucoma, and to find out if potential mitochondrial enhancing therapies such as Vitamin B3 can restore mitochondrial function in fibroblasts from such patients.
Methods :
We used the ‘Seahorse’ extracellular flux analyser to measure oxygen consumption of plated fibroblasts in order to derive their mitochondrial function. In our first experiment we analysed fibroblasts from normal tension glaucoma patients (n=7) and age similar controls (n=7) to compare their mitochondrial function. In our second experiment, three of these NTG cell lines were randomly selected and treated with 5mM vitamin B3 in medium over a one week period, refreshing the medium three times two days apart. Seahorse was then used to quantify the mitochondrial function.
Results :
In our first experiment to determine differences in basal oxygen consumption rates, control lines (n=7) displayed a rate of 145.9 pmol/min (SE : 29.19), and those for NTG lines (n=7) were 74.2 pmol/min (SE: 8.20), P = 0.044. In our second experiment at baseline without treatment, NTG cell lines (n=3) displayed a basal oxygen consumption rate of 57.4 pmol/min (SE=6.89). After one week of treatment with vitamin B3 this increased to 84.3 pmol/min (SE= 16.35). P = 0.007.
Conclusions :
Fibroblasts from NTG cell lines have statistically significantly poorer mitochondrial function than age-matched controls. Vitamin B3 has the ability to potentiate mitochondrial function in these cells and so may be a viable therapeutic option for the treatment of glaucoma.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.