Neuroprotection in Glaucoma: NAD+/NADH Redox State as a Potential Biomarker and Therapeutic Target.
Bledi PetritiPete A WilliamsGerassimos LascaratosKai-Yin ChauDavid F Garway-HeathPublished in: Cells (2021)
Glaucoma is the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with age and the level of intraocular pressure (IOP). IOP reduction is currently the only therapeutic modality shown to slow glaucoma progression. However, patients still lose vision despite best treatment, suggesting that other factors confer susceptibility. Several studies indicate that mitochondrial function may underlie both susceptibility and resistance to developing glaucoma. Mitochondria meet high energy demand, in the form of ATP, that is required for the maintenance of optimum retinal ganglion cell (RGC) function. Reduced nicotinamide adenine dinucleotide (NAD+) levels have been closely correlated to mitochondrial dysfunction and have been implicated in several neurodegenerative diseases including glaucoma. NAD+ is at the centre of various metabolic reactions culminating in ATP production-essential for RGC function. In this review we present various pathways that influence the NAD+(H) redox state, affecting mitochondrial function and making RGCs susceptible to degeneration. Such disruptions of the NAD+(H) redox state are generalised and not solely induced in RGCs because of high IOP. This places the NAD+(H) redox state as a potential systemic biomarker for glaucoma susceptibility and progression; a hypothesis which may be tested in clinical trials and then translated to clinical practice.
Keyphrases
- optic nerve
- clinical trial
- cataract surgery
- end stage renal disease
- clinical practice
- chronic kidney disease
- ejection fraction
- newly diagnosed
- stem cells
- cell death
- risk assessment
- peritoneal dialysis
- cell therapy
- bone marrow
- optical coherence tomography
- study protocol
- open label
- smoking cessation
- blood brain barrier
- drug induced
- double blind