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      The Role of Nutrition and Nutritional Supplements in Ocular Surface Diseases

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          Abstract

          Dry eye disease (DED) is a multifactorial disease of the ocular surface system whose chore mechanisms are tear film instability, inflammation, tear hyperosmolarity and epithelial damage. In recent years, novel therapies specifically targeting inflammation and oxidative stress are being investigated and used in this field. Therefore, an increasing body of evidence supporting the possible role of different micronutrients and nutraceutical products for the treatment of ocular surface diseases is now available. In the present review, we analyzed in detail the effects on ocular surface of omega-3 fatty acids, vitamins A, B12, C, D, selenium, curcumin and flavonoids. Among these, the efficacy of omega-3 fatty acid supplementation in ameliorating DED signs and symptoms is supported by robust scientific evidence. Further long-term clinical trials are warranted to confirm the safety and efficacy of the supplementation of the other micronutrients and nutraceuticals.

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          Most cited references 101

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          Vitamin B12, folic acid, and the nervous system.

          There are many reasons for reviewing the neurology of vitamin-B12 and folic-acid deficiencies together, including the intimate relation between the metabolism of the two vitamins, their morphologically indistinguishable megaloblastic anaemias, and their overlapping neuropsychiatric syndromes and neuropathology, including their related inborn errors of metabolism. Folates and vitamin B12 have fundamental roles in CNS function at all ages, especially the methionine-synthase mediated conversion of homocysteine to methionine, which is essential for nucleotide synthesis and genomic and non-genomic methylation. Folic acid and vitamin B12 may have roles in the prevention of disorders of CNS development, mood disorders, and dementias, including Alzheimer's disease and vascular dementia in elderly people.
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            Is Open Access

            Flavonoid Bioavailability and Attempts for Bioavailability Enhancement

            Flavonoids are a group of phytochemicals that have shown numerous health effects and have therefore been studied extensively. Of the six common food flavonoid classes, flavonols are distributed ubiquitously among different plant foods whereas appreciable amounts of isoflavones are found in leguminous plant-based foods. Flavonoids have shown promising health promoting effects in human cell culture, experimental animal and human clinical studies. They have shown antioxidant, hypocholesterolemic, anti-inflammatory effects as well as ability to modulate cell signaling and gene expression related disease development. Low bioavailability of flavonoids has been a concern as it can limit or even hinder their health effects. Therefore, attempts to improve their bioavailability in order to improve the efficacy of flavonoids are being studied. Further investigations on bioavailability are warranted as it is a determining factor for flavonoid biological activity.
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              TFOS DEWS II pain and sensation report

              Pain associated to mechanical and chemical irritation of the eye surface is mediated by trigeminal ganglia mechano- and polymodal nociceptor neurons while cold thermoreceptors detect wetness and reflexly maintain basal tear production and blinking rate. These neurons project into two regions of the trigeminal brain stem nuclear complex: ViVc, activated by changes in the moisture of the ocular surface and VcC1, mediating sensory-discriminative aspects of ocular pain and reflex blinking. ViVc ocular neurons project to brain regions that control lacrimation and spontaneous blinking and to the sensory thalamus. Secretion of the main lacrimal gland is regulated dominantly by autonomic parasympathetic nerves, reflexly activated by eye surface sensory nerves. These also evoke goblet cell secretion through unidentified efferent fibers. Neural pathways involved in the regulation of Meibonian gland secretion or mucins release have not been identified. In dry eye disease, reduced tear secretion leads to inflammation and peripheral nerve damage. Inflammation causes sensitization of polymodal and mechano-nociceptor nerve endings and an abnormal increase in cold thermoreceptor activity, altogether evoking dryness sensations and pain. Long-term inflammation and nerve injury alter gene expression of ion channels and receptors at terminals and cell bodies of trigeminal ganglion and brainstem neurons, changing their excitability, connectivity and impulse firing. Perpetuation of molecular, structural and functional disturbances in ocular sensory pathways ultimately leads to dysestesias and neuropathic pain referred to the eye surface. Pain can be assessed with a variety of questionaires while the status of corneal nerves is evaluated with esthesiometry and with in vivo confocal microscopy.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                30 March 2020
                April 2020
                : 12
                : 4
                Affiliations
                [1 ]Ophthalmology Unit, S.Orsola-Malpighi University Hospital, University of Bologna, 40138 Bologna, Italy; c.senni3@ 123456gmail.com (C.S.); federico.bernabei89@ 123456gmail.com (F.B.)
                [2 ]Medical and Surgical Sciences Department, University of Bologna, 40138 Bologna, Italy; arrigo.cicero@ 123456unibo.it
                [3 ]Eye Clinic of Genoa, Policlinico San Martino, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, 16132 Genoa, Italy; aldo.vagge@ 123456gmail.com
                [4 ]Medical Oncology Department, Santa Maria della Scaletta Hospital, 40026 Imola, Italy; a.maestri@ 123456ausl.imola.bo.it
                [5 ]Department of Ophthalmology, University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy; vscorcia@ 123456libero.it (V.S.); giuseppe.giannaccare@ 123456gmail.com (G.G.)
                Author notes
                [* ]Correspondence: marco.pellegrini@ 123456hotmail.it ; Tel.: +39-3343-308141
                Article
                nutrients-12-00952
                10.3390/nu12040952
                7230622
                32235501
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                Categories
                Review

                Nutrition & Dietetics

                ocular surface, dry eye disease, nutritional supplements, nutraceuticals

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