Biochemistry and Molecular Biology Developmentally Regulated Production of meso- Zeaxanthin in Chicken Retinal Pigment Epithelium/ Choroid and Retina

PURPOSE. meso-Zeaxanthin is a carotenoid that is rarely encountered in nature outside of the vertebrate eye. It is not a constituent of a normal human diet, yet this carotenoid comprises onethird of the primate macular pigment. In the current study, we undertook a systematic approach to biochemically characterize the production of meso-zeaxanthin in the vertebrate eye. METHODS. Fertilized White Leghorn chicken eggs were analyzed for the presence of carotenoids during development. Yolk, liver, brain, serum, retina, and RPE/choroid were isolated, and carotenoids were extracted. The samples were analyzed on C-30 or chiral HPLC columns to determine the carotenoid composition. RESULTS. Lutein and zeaxanthin were found in all studied nonocular tissues, but no mesozeaxanthin was ever detected. Among the ocular tissues, the presence of meso-zeaxanthin was consistently observed starting at embryonic day 17 (E17) in the RPE/choroid, several days before its consistent detection in the retina. If RPE/choroid of an embryo was devoid of mesozeaxanthin, the corresponding retina was always negative as well. CONCLUSIONS. This is the first report of developmentally regulated synthesis of mesozeaxanthin in a vertebrate system. Our observations suggest that the RPE/choroid is the primary site of meso-zeaxanthin synthesis. Identification of meso-zeaxanthin isomerase enzyme in the developing chicken embryo will facilitate our ability to determine the biochemical mechanisms responsible for production of this unique carotenoid in other higher vertebrates, such as humans

Lutein and zeaxanthin attenuates VEGF-induced neovascularisation in human retinal microvascular endothelial cells through a Nox4-dependent pathway

Age-related macular degeneration (AMD) and proliferative diabetic retinopathy (DR) are two of the most common and severe causes of vision loss in the population. Both conditions are associated with excessive levels of vascular endothelial growth factor (VEGF) in the eye which results in an increase in the formation of new blood vessels through a process called neovascularisation. As such, anti-VEGF therapies are currently utilised as a treatment for patients with AMD however they are associated with painful administration of injections and potential degeneration of healthy endothelium. There is therefore growing interest in alternate treatment options to reduce neovascularisation in the eye. The use of carotenoids, lutein (L) and zeaxanthin (Z), has been shown to improve vision loss parameters in patients with AMD, however the underlying mechanisms are not well-understood. We studied the impact of these compounds on neovascularisation processes using an in vitro cell model of the retinal microvascular endothelium. Our findings show that L and Z reduced VEGF-induced tube formation whilst, in combination (5:1 ratio), the compounds significantly blocked VEGF-induced neovascularisation. The carotenoids, individually and in combination, reduced VEGF-induced oxidative stress concomitant with increased activity of the NADPH oxidase, Nox4. We further demonstrated that the Nox4 inhibitor, GLX7013114, attenuated the protective effect of L and Z. Taken together, these findings indicate the protective effect of the carotenoids, L and Z, in reducing VEGF-mediated neovascularisation via a Nox4-dependent pathway. These studies implicate the potential for these compounds to be used as a therapeutic approach for patients suffering from AMD and proliferative DR

Antioxidant and oxidative stress: a mutual interplay in age-related diseases

Aging is the progressive loss of organ and tissue function over time. Growing older is positively linked to cognitive and biological degeneration such as physical frailty, psychological impairment, and cognitive decline. Oxidative stress is considered as an imbalance between pro- and antioxidant species, which results in molecular and cellular damage. Oxidative stress plays a crucial role in the development of age-related diseases. Emerging research evidence has suggested that antioxidant can control the autoxidation by interrupting the propagation of free radicals or by inhibiting the formation of free radicals and subsequently reduce oxidative stress, improve immune function, and increase healthy longevity. Indeed, oxidation damage is highly dependent on the inherited or acquired defects in enzymes involved in the redox-mediated signaling pathways. Therefore, the role of molecules with antioxidant activity that promote healthy aging and counteract oxidative stress is worth to discuss further. Of particular interest in this article, we highlighted the molecular mechanisms of antioxidants involved in the prevention of age-related diseases. Taken together, a better understanding of the role of antioxidants involved in redox modulation of inflammation would provide a useful approach for potential interventions, and subsequently promoting healthy longevity

Lutein, zeaxanthin, and meso-zeaxanthin: The basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease

Pušenje je štetna navika raširena među svim slojevima pučanstva. Smatra se rizičnim čimbenikom za zdravlje koji dovodi do prijevremenog umiranja. Duhanski dim sadrži više od četiri tisuće sastojaka koji djelujući podražajno, toksično, kancerogeno i psihoaktivno remete funkcije pojedinih organa. Ne postoji ni jedan organ ili organski sustav koji nije zahvaćen štetnim učincima pušenja. U ovom radu opisano je djelovanje duhanskog dima na krvožilni, dišni i probavni sustav. Također su spomenute i opasnosti pasivnog pušenja. Naglašena je važnost zdravstvenog odgoja te su razrađene metode zdravstvenog odgoja kojima se ovisnicima o pušenju nastoji promijeniti štetno zdravstveno ponašanje. Posebno je naglašena važnost medicinske sestre koja svojim znanjem i osobnim primjerom ima veliki utjecaj na smanjenje uporabe duhana kod pojedinca i zajednice. Opisan je pristup medicinske sestre kod određenih skupina kao što su trudnice, djeca i mladi te starije osobe.Smoking is a harmful habit widespread among all sections of the population. It is considered a risk factor for health leading to premature death. Tobacco smoke contains more than four thousand ingredients that have an irritant, toxic, carcinogenic and psychoactive effect on the functions of individual organs. There is no organ or organ system that is not affected by the harmful effects of smoking. This paper describes the effect of tobacco smoke on the circulatory, respiratory and digestive systems. The dangers of secondhand smoke were also mentioned. The importance of health education is emphasized and methods of health education that seek to change addictive behaviors are elaborated. Particular emphasis is placed on the importance of the nurse, who with her knowledge and personal example has a great influence on reducing the use of tobacco in individuals and in the community. The approach of the nurse to specific groups such as pregnant women, children and young people and the elderly is described

Membrane cholesterol regulates TRPV4 function, cytoskeletal expression, and the cellular response to tension

Despite the association of cholesterol with debilitating pressure-related diseases such as glaucoma, heart disease, and diabetes, its role in mechanotransduction is not well understood. We investigated the relationship between mechanical strain, free membrane cholesterol, actin cytoskeleton, and the stretch-activated transient receptor potential vanilloid isoform 4 (TRPV4) channel in human trabecular meshwork (TM) cells. Physiological levels of cyclic stretch resulted in time-dependent decreases in membrane cholesterol/phosphatidylcholine ratio and upregulation of stress fibers. Depleting free membrane cholesterol with m-β-cyclodextrin (MβCD) augmented TRPV4 activation by the agonist GSK1016790A, swelling and strain, with the effects reversed by cholesterol supplementation. MβCD increased membrane expression of TRPV4, caveolin-1, and flotillin. TRPV4 did not colocalize or interact with caveolae or lipid rafts, apart from a truncated ∼75 kDa variant partially precipitated by a caveolin-1 antibody. MβCD induced currents in TRPV4-expressing Xenopus laevis oocytes. Thus, membrane cholesterol regulates trabecular transduction of mechanical information, with TRPV4 channels mainly located outside the cholesterol-enriched membrane domains. Moreover, the biomechanical milieu itself shapes the lipid content of TM membranes. Diet, cholesterol metabolism, and mechanical stress might modulate the conventional outflow pathway and intraocular pressure in glaucoma and diabetes in part by modulating TM mechanosensing