New solutions for old challenges in glaucoma treatment:is taurine an option to consider?

Glaucoma is a range of progressive optic neuropathies characterized by progressive retinal ganglion cell loss and visual field defects.It is recognized as a leading cause of irreversible blindness affecting more than 70 million people worldwide.Currently,reduction of intraocular pressure,a widely recognized risk factor for glaucoma development,is the only pharmacological strategy for slowing down retinal ganglion cell loss and disease progression.However,retinal ganglion cell death and visual field loss have been observed in normotensive glaucoma,suggesting that the disease process is partially independent of intraocular pressure.Taurine is one of the agents that have attracted attention of researchers recently.Taurine has been shown to be involved in multiple cellular functions,including a central role as a neurotransmitter,as a trophic factor in the central nervous system development,as an osmolyte,as a neuromodulator,and as a neuroprotectant.It also plays a role in the maintenance of the structural integrity of the membranes and in the regulation of calcium transport and homeostasis.Taurine is known to prevent N-methyl-D-aspartic acid-induced excitotoxic injury to retinal ganglion cells.A recently published study clearly demonstrated that taurine prevents retinal neuronal apoptosis both in vivo and in vitro.Protective effect of taurine may be attributed to direct inhibition of apoptosis,an activation of brain derived neurotrophic factor-related neuroprotective mechanisms and reduction of retinal oxidative and nitrosative stresses.Further studies are needed to fully explore the potential of taurine as a neuroprotective agent,so that it can be applied in clinical practice,particularly for the treatment of glaucoma.The objective of current review was to summarize recent evidence on neuroprotective properties of taurine in glaucoma.

False dogmas in mood disorders research:Towards a nomothetic network approach

The current understanding of major depressive disorder(MDD)and bipolar disorder(BD)is plagued by a cacophony of controversies as evidenced by competing schools to understand MDD/BD.The DSM/ICD taxonomies have cemented their status as the gold standard for diagnosing MDD/BD.The aim of this review is to discuss the false dogmas that reign in current MDD/BD research with respect to the new,data-driven,machine learning method to model psychiatric illness,namely nomothetic network psychiatry(NNP).This review discusses many false dogmas including:MDD/BD are mind-brain disorders that are best conceptualized using a bio-psycho-social model or mind-brain interactions;mood disorders due to medical disease are attributable to psychosocial stress or chemical imbalances;DSM/ICD are the gold standards to make the MDD/BD diagnosis;severity of illness should be measured using rating scales;clinical remission should be defined using threshold values on rating scale scores;existing diagnostic BD boundaries are too restrictive;and mood disorder spectra are the rule.In contrast,our NNP models show that MDD/BD are not mind-brain or psycho-social but systemic medical disorders;the DSM/ICD taxonomies are counterproductive;a shared core,namely the reoccurrence of illness(ROI),underpins the intertwined recurrence of depressive and manic episodes and suicidal behaviors;mood disorders should be ROI-defined;ROI mediates the effects of nitro-oxidative stress pathways and early lifetime trauma on the phenome of mood disorders;severity of illness and treatment response should be delineated using the NNP-derived causome,pathway,ROI and integrated phenome scores;and MDD and BD are the same illness.

Redox regulation of the immune response

The immune-inflammatory response is associated with increased nitro-oxidative stress.The aim of this mechanistic review is to examine:(a)the role of redox-sensitive transcription factors and enzymes,ROS/RNS production,and the activity of cellular antioxidants in the activation and performance of macrophages,dendritic cells,neutrophils,T-cells,B-cells,and natural killer cells;(b)the involvement of high-density lipoprotein(HDL),apolipoprotein A1(ApoA1),paraoxonase-1(PON1),and oxidized phospholipids in regulating the immune response;and(c)the detrimental effects of hypernitrosylation and chronic nitro-oxidative stress on the immune response.The redox changes during immune-inflammatory responses are orchestrated by the actions of nuclear factor-κB,HIF1α,the mechanistic target of rapamycin,the phosphatidylinositol 3-kinase/protein kinase B signaling pathway,mitogen-activated protein kinases,5'AMP-activated protein kinase,and peroxisome proliferator-activated receptor.The performance and survival of individual immune cells is under redox control and depends on intracellular and extracellular levels of ROS/RNS.They are heavily influenced by cellular antioxidants including the glutathione and thioredoxin systems,nuclear factor erythroid 2-related factor 2,and the HDL/ApoA1/PON1 complex.Chronic nitro-oxidative stress and hypernitrosylation inhibit the activity of those antioxidant systems,the tricarboxylic acid cycle,mitochondrial functions,and the metabolism of immune cells.In conclusion,redox-associated mechanisms modulate metabolic reprogramming of immune cells,macrophage and T helper cell polarization,phagocytosis,production of pro-versus anti-inflammatory cytokines,immune training and tolerance,chemotaxis,pathogen sensing,antiviral and antibacterial effects,Toll-like receptor activity,and endotoxin tolerance.