Peripheral blood mononuclear cell respiratory function is associated with progressive glaucomatous vision loss

Intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma and all licensed treatments lower IOP. However, many patients continue to lose vision despite IOP-lowering treatment. Identifying biomarkers for progressive vision loss would have considerable clinical utility. We demonstrate that lower peripheral blood mononuclear cell (PBMC) oxygen consumption rate (OCR) is strongly associated with faster visual field (VF) progression in patients treated by lowering IOP (P < 0.001, 229 eyes of 139 participants), explaining 13% of variance in the rate of progression. In a separate reference cohort of untreated patients with glaucoma (213 eyes of 213 participants), IOP explained 16% of VF progression variance. OCR is lower in patients with glaucoma (n = 168) than in controls (n = 50; P < 0.001) and is lower in patients with low baseline IOP (n = 99) than those with high baseline IOP (n = 69; P < 0.01). PBMC nicotinamide adenine dinucleotide (NAD) levels are lower in patients with glaucoma (n = 29) compared to controls (n = 25; P < 0.001) and strongly associated with OCR (P < 0.001). Our results support PBMC OCR and NAD levels as new biomarkers for progressive glaucoma

The Role of Mitophagy in Glaucomatous Neurodegeneration

This review aims to provide a better understanding of the emerging role of mitophagy in glaucomatous neurodegeneration, which is the primary cause of irreversible blindness worldwide. Increasing evidence from genetic and other experimental studies suggests that mitophagy-related genes are implicated in the pathogenesis of glaucoma in various populations. The association between polymorphisms in these genes and increased risk of glaucoma is presented. Reduction in intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma, while clinical trials highlight the inadequacy of IOP-lowering therapeutic approaches to prevent sight loss in many glaucoma patients. Mitochondrial dysfunction is thought to increase the susceptibility of retinal ganglion cells (RGCs) to other risk factors and is implicated in glaucomatous degeneration. Mitophagy holds a vital role in mitochondrial quality control processes, and the current review explores the mitophagy-related pathways which may be linked to glaucoma and their therapeutic potential

Neuroprotection in Glaucoma: NAD(+)/NADH Redox State as a Potential Biomarker and Therapeutic Target

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

Salivary analysis to unveil the paradigma of stress of domestic horses reared in the wild

Abstract Horse welfare is the product of multiple factors, including behavioral and physiological adjustments to cope with stressful situation regarding environment and housing condition. Collectively, it is supposed that a horse kept in the wild has a lower level of stress than other housing system, and the aim of the present study was to investigate the level of stress in domestic horses reared in the wild and then moved to human controlled housing, through saliva analysis. Twelve clinically healthy Catria (Italian local breed) mares, usually reared in the wild, were moved into collective paddocks for a folkloric event. Saliva samples were obtained before and after the change of housing condition to evaluate stress biomarkers including salivary cortisol, salivary alpha-amylase, and butyrylcholinesterase (BChol). The mares were also scored using the Welfare Aggregation and Guidance (WAG) Tool to highlight the presence of abnormal behaviors. Despite the absence of differences in behavioral scores between wild and paddocks, salivary cortisol and BChol were found to be higher in the wild and lower when mares were moved to paddocks. The highest concentrations in stress biomarkers like salivary cortisol and BChol in the wild was unexpected, but the need for managing hierarchical relationships, and the exposure to feral animals, predators, and weather changes, might explain these findings. The overall results of the present study may provide further knowledge toward stress response in domesticated horses living in the wild moved to human controlled housing system