This review will discuss some issues related to the risk/benefit profile of the use of dietary antioxidants. Thus, recent progress regarding the potential benefit of dietary antioxidants in the treatment of chronic diseases with a special focus on immune system and neurodegenerative disorders will be discussed here. It is well established that reactive oxygen species (ROS) play an important role in the etiology of numerous diseases, such as atherosclerosis, diabetes and cancer. Among the physiological defense system of the cell, the relevance of antioxidant molecules, such as glutathione and vitamins is quite well established. Recently, the interest of researchers has, for example, been conveyed on antioxidant enzyme systems, such as the heme oxygenase/biliverdin reductase system, which appears modulated by dietary antioxidant molecules, including polyphenols and beta-carotene. These systems possibly counteract oxidative damage very efficiently and finally modulate the activity of oxidative phenomena occurring, for instance, during pathophysiological processes. Although evidence shows that antioxidant treatment results in cytoprotection, the potential clinical benefit deriving from both nutritional and supplemental antioxidants is still under wide debate. In this line, the inappropriate assumption of some lipophylic vitamins has been associated with increased incidence of cancer rather than with beneficial effects.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent, multifactorial, and poorly understood liver disease with an increasing incidence worldwide. NAFLD is typically asymptomatic and coupled with other symptoms of metabolic syndrome. The prevalence of NAFLD is rising in tandem with the prevalence of obesity. In the Western hemisphere, NAFLD is one of the most prevalent causes of liver disease and liver transplantation. Recent research suggests that gut microbiome dysbiosis may play a significant role in the pathogenesis of NAFLD by dysregulating the gut–liver axis. The so-called “gut–liver axis” refers to the communication and feedback loop between the digestive system and the liver. Several pathological mechanisms characterized the alteration of the gut–liver axis, such as the impairment of the gut barrier and the increase of the intestinal permeability which result in endotoxemia and inflammation, and changes in bile acid profiles and metabolite levels produced by the gut microbiome. This review will explore the role of gut–liver axis disruption, mediated by gut microbiome dysbiosis, on NAFLD development.

To investigate the effects of gabapentin, a structural analogue of γ-amino butyric acid (GABA), on the inflammatory response of lipopolysaccharide (LPS)‑stimulated rabbit corneal cells (SIRC) and on endotoxin-induced uveitis (EIU) in rabbits. We investigated the LPS-induced expression of several inflammatory mediators, such as TNF-α, IL-1β, cPLA2, COX-2 and PGE2 in the SIRC cells with or without gabapentin treatment. Gabapentin treatment significantly (p<0.05) attenuated cytokines production, cPLA2 activation, COX-2 expression and PGE2 levels in SIRC. EIU was induced by an intraocular injection of 0.1 μg of LPS in albino rabbit eye. After 7 and 24 hours from LPS injection clinical signs of ocular inflammation were examined by slit lamp with or without topical treatment of 0.5% gabapentin. Tears, aqueous, cornea, conjunctiva and iris-ciliary body were collected and inflammatory biomarkers assessed. Topical treatment with gabapentin significantly (p<0.05) reduced clinical signs and biomarkers of inflammation compared with the LPS group both at 7 and 24 hours. In conclusion, the results generated in the present study suggest that ophthalmic formulation based on gabapentin may be useful in the treatment of inflammatory conditions associated to ocular pain such as uveitis, and that clinical studies to evaluate this possibility may be warranted.

The rate at which obesity is becoming an epidemic in many countries is alarming. Obese individuals have a high risk of developing elevated intraocular pressure and glaucoma. Additionally, glaucoma is a disease of epidemic proportions. It is characterized by neurodegeneration and neuroinflammation with optic neuropathy and the death of retinal ganglion cells (RGC). On the other hand, there is growing interest in microbiome dysbiosis, particularly in the gut, which has been widely acknowledged to play a prominent role in the etiology of metabolic illnesses such as obesity. Recently, studies have begun to highlight the fact that microbiome dysbiosis could play a critical role in the onset and progression of several neurodegenerative diseases, as well as in the development and progression of several ocular disorders. In obese individuals, gut microbiome dysbiosis can induce endotoxemia and systemic inflammation by causing intestinal barrier malfunction. As a result, bacteria and their metabolites could be delivered via the bloodstream or mesenteric lymphatic vessels to ocular regions at the level of the retina and optic nerve, causing tissue degeneration and neuroinflammation. Nowadays, there is preliminary evidence for the existence of brain and intraocular microbiomes. The altered microbiome of the gut could perturb the resident brain–ocular microbiome ecosystem which, in turn, could exacerbate the local inflammation. All these processes, finally, could lead to the death of RGC and neurodegeneration. The purpose of this literature review is to explore the recent evidence on the role of gut microbiome dysbiosis and related inflammation as common mechanisms underlying obesity and glaucoma.

Background: The etiology and the mechanism behind atropine treatment of progressive myopia are still poorly understood. Our study addressed the role of scleral and choroidal fibroblasts in myopia development and atropine function. Methods: Fibroblasts treated in vitro with atropine or 7-methylxanthine were tested for ECM production by Western blotting. Corneal epithelial cells were treated with atropine in the presence or absence of colostrum or fucosyl-lactose, and cell survival was evaluated by the MTT metabolic test. Results: Atropine and 7-methyl-xanthine stimulated collagen I and fibronectin production in scleral fibroblasts, while they inhibited their production in choroidal fibroblasts. Four days of treatment with atropine of corneal epithelial cells significantly decreased cell viability, which could be prevented by the presence of colostrum or fucosyl-lactose. Conclusions: Our results show that atropine may function in different ways in different eye districts, strengthening the scleral ECM and increasing permeability in the choroid. The finding that colostrum or fucosyl-lactose attenuate the corneal epithelial toxicity after long-term atropine treatment suggests the possibility that both compounds can efficiently blunt its toxicity in children subjected to chronic atropine treatment.

Melatonin is of great importance for regulating several eye processes, including pressure homeostasis. Melatonin in combination with agomelatine has been recently reported to reduce intraocular pressure (IOP) with higher efficacy than each compound alone. Here, we used the methylcellulose (MCE) rat model of hypertensive glaucoma, an optic neuropathy characterized by the apoptotic death of retinal ganglion cells (RGCs), to evaluate the hypotensive and neuroprotective efficacy of an eye drop nanomicellar formulation containing melatonin/agomelatine. Eye tissue distribution of melatonin/agomelatine in healthy rats was evaluated by HPLC/MS/MS. In the MCE model, we assessed by tonometry the hypotensive efficacy of melatonin/agomelatine. Neuroprotection was revealed by electroretinography; by levels of inflammatory and apoptotic markers; and by RGC density. The effects of melatonin/agomelatine were compared with those of timolol (a beta blocker with prevalent hypotensive activity) or brimonidine (an alpha 2 adrenergic agonist with potential neuroprotective efficacy), two drugs commonly used to treat glaucoma. Both melatonin and agomelatine penetrate the posterior segment of the eye. In the MCE model, IOP elevation was drastically reduced by melatonin/agomelatine with higher efficacy than that of timolol or brimonidine. Concomitantly, gliosis-related inflammation and the Bax-associated apoptosis were partially prevented, thus leading to RGC survival and recovered retinal dysfunction. We suggest that topical melatoninergic compounds might be beneficial for ocular health.