Diabetes mellitus is a common metabolic disorder associated with chronic complications including a state of mild to moderate cognitive impairment, in particular psychomotor slowing and reduced mental flexibility, not attributable to other causes, and shares many symptoms that are best described as accelerated brain ageing. A common theory for aging and for the pathogenesis of this cerebral dysfunctioning in diabetes relates cell death to oxidative stress in strong association to inflammation, and in fact nuclear factorκB (NFκB), a master regulator of inflammation and also a sensor of oxidative stress, has a strategic position at the crossroad between oxidative stress and inflammation. Moreover, metabolic inflammation is, in turn, related to the induction of various intracellular stresses such as mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, and autophagy defect. In parallel, blockade of autophagy can relate to proinflammatory signaling via oxidative stress pathway and NFκB-mediated inflammation.

A major pathogenic mechanism of chronic alcoholism involves oxidative burden to liver and other cell types. We show that adult neurogenesis within the dentate gyrus of the hippocampus is selectively impaired in a rat model of alcoholism, and that it can be completely prevented by the antioxidant ebselen. Rats fed for 6 weeks with a liquid diet containing moderate doses of ethanol had a 66.3% decrease in the number of new neurons and a 227–279% increase in cell death in the dentate gyrus as compared with paired controls. Neurogenesis within the olfactory bulb was not affected by alcohol. Our studies indicate that alcohol abuse, even for a short duration, results in the death of newly formed neurons within the adult brain and that the underlying mechanism is related to oxidative or nitrosative stress. Moreover, these findings suggest that the impaired neurogenesis may be a mechanism mediating cognitive deficits observed in alcoholism.

The retinal pigment epithelium ( RPE ), a monolayer located between the photoreceptors and the choroid, is constantly damaged by oxidative stress, particularly because of reactive oxygen species ( ROS ). As the RPE , because of its physiological functions, is essential for the survival of the retina, any sustained damage may consequently lead to loss of vision. Exosomes are small membranous vesicles released into the extracellular medium by numerous cell types, including RPE cells. Their cargo includes genetic material and proteins, making these vesicles essential for cell‐to‐cell communication. Exosomes may fuse with neighbouring cells influencing their fate. It has been observed that RPE cells release higher amounts of exosomes when they are under oxidative stress. Exosomes derived from cultured RPE cells were isolated by ultracentrifugation and quantified by flow cytometry. VEGF receptors ( VEGFR ) were analysed by both flow cytometry and Western blot. RT ‐ PCR and qPCR were conducted to assess mRNA content of VEGFR s in exosomes. Neovascularization assays were performed after applying RPE exosomes into endothelial cell cultures. Our results showed that stressed RPE cells released a higher amount of exosomes than controls, with a higher expression of VEGFR in the membrane, and enclosed an extra cargo of VEGFR mRNA . Angiogenesis assays confirmed that endothelial cells increased their tube formation capacity when exposed to stressed RPE exosomes.

Purpose.: The purpose of this study was to establish the alterations of oxidative stress-related markers in keratoconus (KC) corneas. Methods.: A total of 6 healthy and 11 ectatic corneas (7 KC and 4 post-LASIK) were studied. Different oxidative stress-related markers were determined to assess their implication in the KC pathophysiology. Total antioxidant capacity and total nitrites present in the samples were assayed. Furthermore, lipid peroxidation products and the glutathione contents were determined, together with 4-hydroxynonenal (4-HNE) immunohistochemistry, to establish the relationship between KC and oxidative stress. Results.: The antioxidant capacity and glutathione content in KC corneas were decreased significantly when compared with healthy corneas. Moreover, the total nitrites and lipid peroxidation were significantly elevated in the corneas with KC when compared with the controls. There was a statistically significant difference in the amount of HNE-positive cells in KC corneas when compared with healthy corneas by immunohistochemistry. Post-LASIK ectatic corneas and KC corneas showed similar results. Conclusions.: The increased levels of oxidative stress markers and the decreased antioxidant capacity and antioxidant defenses in KC corneas, as well as in the post-LASIK ectatic corneas, indicate that oxidative stress might be involved in the development of this disease and may provide new insights for its prevention and treatment in the future.