Glauoma, B3 and pyruvate

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2786482 

Introduction

Randomized clinical trials in glaucoma have demonstrated that lowering intraocular pressure (IOP) is associated with reduced risk of glaucoma onset and progression across the disease spectrum, regardless of severity.1-6 However, glaucoma continued to progress in many individuals despite significant IOP reduction, a finding also commonly seen in clinical practice. 

The consensus opinion of the authors is that this is owing to either insufficient lowering of IOP, IOP-independent risk factors, or a combination of the two.3,7,8 In an effort to further protect retinal ganglion cells (RGCs) and their axons, recent studies have investigated the association between nutritional biomarkers and the risk of glaucoma9,10 as well as the potential benefit of nutritional supplementation on measures of visual function.10-13

Mitochondrial abnormalities may be an early driver of neuronal dysfunction in glaucoma.14 In the DBA/2J mouse model (studying inherited, chronic, elevated IOP and glaucoma in mice) and in an inducible model of ocular hypertension in rats, these mitochondrial and metabolic changes occurred even before detectable neurodegeneration.15,16 In particular, investigators have reported that oral administration of nicotinamide (the amide of vitamin B3 and a precursor for nicotinamide adenine dinucleotide [NAD], a key molecule in energy and redox metabolism) was neuroprotective in the DBA/2J model. 

At the highest dose tested, 93% of eyes in DBA/2J did not develop glaucoma, as determined by the absence of RGC somal and axonal loss.15 Given the decrease in NAD with aging,15,17 which may render retinal neurons more vulnerable to disease-related insults, the investigators hypothesized that increasing NAD may support the mitochondrial activity of RGCs and decrease their susceptibility to glaucoma.18-21

 In a rat model of ocular hypertension, retinal and optic nerve NAD declined as a function of IOP, while nicotinamide was neuroprotective at a range of doses.16 In addition, nicotinamide has been shown to be low in the sera of patients with primary open-angle glaucoma.10 These data further support a role for NAD in glaucoma. 

Furthermore, Harder et al22 reported that an IOP-mediated decrease in retinal pyruvate levels was associated with dysregulated glucose metabolism prior to detectable optic nerve degeneration in metabolic studies of DBA/2J mice. They also found that oral supplementation with pyruvate protected both rat and mouse models of glaucoma from neurodegeneration, with a combination of nicotinamide and pyruvate being the most protective in the chronic mouse model.