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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Public Health".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 83560

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Prof. Dr. Paola Bagnoli

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Guest Editor

Department of Biology, University of Pisa, 56127 Pisa, Italy
Interests: animal models; ocular diseases; retinal function; neurodegeneration; neuroprotection; angiogenesis; inflammation; anti-angiogenic and anti-inflammatory compounds; dietary supplementation; eye health
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Special Issue Information

Dear Colleagues,

Among ocular diseases, those that substantially affect the vision by disrupting the functioning of retinal neurons represent a major burden with a high social and economic impact. In particular, visual impairment exacts an enormous financial and social cost on developing countries, thus requiring much research work into the cause and prevention of major blinding diseases. In addition to pharmacological therapies, the management of ocular pathologies includes nutritional supplements such as antioxidants, vitamins or fatty acids that are at present extensively investigated in terms of prophylactic benefits, potential harm, and optimal use. For instance, naturally occurring substances that humans take in with a normal diet can serve as antioxidants and free radical scavengers, possibly reducing or eliminating tissue damage from oxidation or the presence of free radicals in those tissues. However, evidence for the benefit of diet supplementation is often controversial. For instance, epidemiological studies have indicated potential preventive effects of omega-3 fatty acids against dry AMD, although the results of the Age-Related Disease Study 2 (AREDS2) seem to exclude their potential in preventing AMD progression. An additional complication in the use of nutraceuticals as therapeutic strategies is their scarce oral bioavailability, thus rendering investigations aimed to improve this aspect of fundamental importance.

This Special Issue collects reviews or original papers representing the state of the art on nutrition and eye health in terms of clinically relevant animal models through which to understand the mechanisms underlying the efficacy of diet supplementation. In addition to preclinical studies, attempts to give an overview of the clinical investigation of dietary supplementation as a potential treatment for ocular pathologies are also recommended.

Prof. Paola Bagnoli
Guest Editor

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Keywords

Animal models of ocular diseases
Anterior chamber
Choroid
Retina
Inflammation
Neurodegeneration
Neuroprotection
Dietary supplementation
Protective mechanisms

Published Papers (14 papers)

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Research

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17 pages, 4740 KiB

Open AccessArticle

Retinal Neurodegeneration: Correlation between Nutraceutical Treatment and Animal Model

by Ilaria Piano, Mattia Di Paolo, Francesca Corsi, Eugenia Piragine, Silvia Bisti, Claudia Gargini and Stefano Di Marco

Nutrients 2021, 13(3), 770; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13030770 - 27 Feb 2021

Cited by 10 | Viewed by 2412

Abstract

Retinal diseases can be induced by a variety of factors, including gene mutations, environmental stresses and dysmetabolic processes. The result is a progressive deterioration of visual function, which sometimes leads to blindness. Many treatments are under investigation, though results are still mostly unsatisfactory and restricted to specific pathologies, particularly in the case of gene therapy. The majority of treatments have been tested in animal models, but very few have progressed to human clinical trials. A relevant approach is to study the relation between the type of treatments and the degenerative characteristics of the animal model to better understand the effectiveness of each therapy. Here we compare the results obtained from different animal models treated with natural compounds (saffron and naringenin) to anticipate the potentiality of a single treatment in different pathologies. Full article

(This article belongs to the Special Issue Nutrition for Eye Health)

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24 pages, 2667 KiB

Open AccessArticle

A Multi-Omics Approach Identifies Key Regulatory Pathways Induced by Long-Term Zinc Supplementation in Human Primary Retinal Pigment Epithelium

by Eszter Emri, Elod Kortvely, Sascha Dammeier, Franziska Klose, David Simpson, EYE-RISK Consortium, Anneke I. den Hollander, Marius Ueffing and Imre Lengyel

Nutrients 2020, 12(10), 3051; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12103051 - 06 Oct 2020

Cited by 14 | Viewed by 3725

Abstract

In age-related macular degeneration (AMD), both systemic and local zinc levels decline. Elevation of zinc in clinical studies delayed the progression to end-stage AMD. However, the molecular pathways underpinning this beneficial effect are not yet identified. In this study, we used differentiated primary human fetal retinal pigment epithelium (RPE) cultures and long-term zinc supplementation to carry out a combined transcriptome, proteome and secretome analysis from three genetically different human donors. After combining significant differences, we identified the complex molecular networks using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). The cell cultures from the three donors showed extensive pigmentation, development of microvilli and basal infoldings and responded to zinc supplementation with an increase in transepithelial electrical resistance (TEER) (apical supplementation: 443.2 ± 79.3%, basal supplementation: 424.9 ± 116.8%, compared to control: 317.5 ± 98.2%). Significant changes were observed in the expression of 1044 genes, 151 cellular proteins and 124 secreted proteins. Gene set enrichment analysis revealed changes in specific molecular pathways related to cell adhesion/polarity, extracellular matrix organization, protein processing/transport, and oxidative stress response by zinc and identified a key upstream regulator effect similar to that of TGFB1. Full article

(This article belongs to the Special Issue Nutrition for Eye Health)

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19 pages, 4315 KiB

Open AccessArticle

A Dietary Combination of Forskolin with Homotaurine, Spearmint and B Vitamins Protects Injured Retinal Ganglion Cells in a Rodent Model of Hypertensive Glaucoma

by Maurizio Cammalleri, Massimo Dal Monte, Rosario Amato, Paola Bagnoli and Dario Rusciano

Nutrients 2020, 12(4), 1189; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12041189 - 23 Apr 2020

Cited by 27 | Viewed by 4961

Abstract

There is indication that nutritional supplements protect retinal cells from degeneration. In a previous study, we demonstrated that dietary supplementation with an association of forskolin, homotaurine, spearmint extract and B vitamins efficiently counteracts retinal dysfunction associated with retinal ganglion cell (RGC) death caused by optic nerve crush. We extended our investigation on the efficacy of dietary supplementation with the use of a mouse model in which RGC degeneration depends as closely as possible on intraocular pressure (IOP) elevation. In this model, injecting the anterior chamber of the eye with methylcellulose (MCE) causes IOP elevation leading to RGC dysfunction. The MCE model was characterized in terms of IOP elevation, retinal dysfunction as determined by electrophysiological recordings, RGC loss as determined by brain-specific homeobox/POU domain protein 3A immunoreactivity and dysregulated levels of inflammatory and apoptotic markers. Except for IOP elevation, dysfunctional retinal parameters were all recovered by dietary supplementation indicating the involvement of non-IOP-related neuroprotective mechanisms of action. Our hypothesis is that the diet supplement may be used to counteract the inflammatory processes triggered by glial cell activation, thus leading to spared RGC loss and the preservation of visual dysfunction. In this respect, the present compound may be viewed as a potential remedy to be added to the currently approved drug therapies for improving RGC protection. Full article

(This article belongs to the Special Issue Nutrition for Eye Health)

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16 pages, 2348 KiB

Open AccessArticle

The Use of Vitamins and Coenzyme Q10 for the Treatment of Vascular Occlusion Diseases Affecting the Retina

by Beatriz Fernández-Vega, Javier Nicieza, Ana Álvarez-Barrios, Lydia Álvarez, Montserrat García, Carlos Fernández-Vega, José A. Vega and Héctor González-Iglesias

Nutrients 2020, 12(3), 723; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12030723 - 09 Mar 2020

Cited by 11 | Viewed by 6762

Abstract

Nutritional supplementation with antioxidants and vitamins is widely recommended in the treatment of vascular disorders affecting the retina, although there is insufficient evidence on its effectiveness. The vitamin-like compound coenzyme Q10 (CoQ10) is a nutritional supplement of current interest to treat neurodegenerative diseases. Here, we report a retrospective clinical case series study of 48 patients diagnosed with retinal vascular diseases, including non-arteritic ischemic optic neuropathy (NAION), retinal artery occlusion (RAO), and homonymous hemianopia or quadrantanopia following stroke, treated with oral supplementation with CoQ10 (100 mg per day) and vitamins. Patient follow-up was performed using the Humphrey field analyzer and 30-2 testing algorithm to determine the visual field index (VFI) and progression rates. All treated patients showed positive VFI progression rates per year: +11.5 ± 15% for NAION patients (n = 18), +22 ± 17% for RAO patients (n = 7), +9.3 ± 10.5% for hemianopia/quadrantanopia patients (n = 10), and +11 ± 21% for patients with other conditions (n = 13). The interruption of CoQ10 supplementation in one patient resulted in a pronounced decrease of the VFI, which was partially recovered when treatment was restored. This study supports the role of CoQ10 as a nutritional therapeutic agent for vascular diseases affecting the retina. Owing to decreased VFI after interruption of CoQ10, its beneficial effects may be reversible. Full article

(This article belongs to the Special Issue Nutrition for Eye Health)

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11 pages, 794 KiB

Open AccessArticle

Maternal Lutein and Zeaxanthin Concentrations in Relation to Offspring Visual Acuity at 3 Years of Age: The GUSTO Study

by Jun S. Lai, Vaishnavi O. Veetil, Carla Lanca, Bee Lan Lee, Keith M. Godfrey, Peter D. Gluckman, Lynette P. Shek, Fabian Yap, Kok Hian Tan, Yap Seng Chong, Choon Nam Ong, Cheryl S Ngo, Seang-Mei Saw and Mary F. F. Chong

Nutrients 2020, 12(2), 274; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12020274 - 21 Jan 2020

Cited by 14 | Viewed by 4052

Abstract

Lutein and zeaxanthin play important roles in visual functions, but their influence on early visual development is unclear. We related maternal lutein and zeaxanthin concentrations during pregnancy to offspring visual acuity (VA) in 471 mother–child pairs from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Maternal concentrations of plasma lutein and zeaxanthin were determined at delivery. We measured uncorrected distance of VA in 3-year old children using a LEA Symbols chart; readings were converted to the logarithm of Minimum Angle of Resolution (logMAR), with >0.3 logMAR indicating poor VA. Associations were examined using linear or Poisson regression adjusted for confounders. The median (inter-quartile range) of maternal lutein and zeaxanthin concentrations were 0.13 (0.09, 0.18) and 0.09 (0.07, 0.12) µmol/L, respectively. A total of 126 children had poor VA. The highest tertile of maternal zeaxanthin concentration was associated with 38% lower likelihood of poor VA in children (95% CI: 0.42, 0.93, p-Trends = 0.02). Higher maternal lutein concentrations were associated with a lower likelihood of poor VA in children (RR 0.60 (95% CI: 0.40, 0.88) for middle tertile; RR 0.78 (95% CI: 0.51, 1.19) for highest tertile (p-Quadratic = 0.02)). In conclusion, lutein and zeaxanthin status during pregnancy may influence offspring early visual development; but the results require confirmation with further studies, including more comprehensive measurements of macular functions. Full article

(This article belongs to the Special Issue Nutrition for Eye Health)

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8 pages, 877 KiB

Open AccessArticle

Estimation of the Minimum Effective Dose of Dietary Supplement Crocetin for Prevention of Myopia Progression in Mice

by Kiwako Mori, Toshihide Kurihara, Xiaoyan Jiang, Shin-ichi Ikeda, Erisa Yotsukura, Hidemasa Torii and Kazuo Tsubota

Nutrients 2020, 12(1), 180; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12010180 - 09 Jan 2020

Cited by 2 | Viewed by 3711

Abstract

The natural carotenoid crocetin has been reported to suppress phenotypes of an experimental myopia model in mice. We investigated the minimum effective dose to prevent myopia progression in a murine model. Three-week-old male mice (C57B6/J) were equipped with a −30 diopter (D) lens to induce myopia, and fed with normal chow, 0.0003%, or 0.001% of crocetin-containing chow. Changes in refractive errors and axial lengths (AL) were evaluated after three weeks. Pharmacokinetics of crocetin in the plasma and the eyeballs of mice was evaluated with specific high sensitivity quantitative analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine the minimum effective dosage. A concentration of 0.001% of crocetin-containing chow showed a significant (p < 0.001) suppressive effect against both refractive and AL changes in the murine model. Meanwhile, there was no significant difference of AL change between the 0.0003% and the normal chow groups. The concentration of crocetin in the plasma and the eyeballs from mice fed with 0.001% crocetin-containing chow was significantly higher than control and 0.0003% crocetin-containing chow. In conclusion, we suggest 0.001% of crocetin-containing extract is the minimum effective dose showing a significant suppressive effect against both refractive and AL changes in the murine model. Full article

(This article belongs to the Special Issue Nutrition for Eye Health)

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Review

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26 pages, 716 KiB

Open AccessReview

The Benefits of Flavonoids in Diabetic Retinopathy

by Ana L. Matos, Diogo F. Bruno, António F. Ambrósio and Paulo F. Santos

Nutrients 2020, 12(10), 3169; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12103169 - 16 Oct 2020

Cited by 35 | Viewed by 4991

Abstract

Diabetic retinopathy (DR), one of the most common complications of diabetes, is the leading cause of legal blindness among adults of working age in developed countries. After 20 years of diabetes, almost all patients suffering from type I diabetes mellitus and about 60% of type II diabetics have DR. Several studies have tried to identify drugs and therapies to treat DR though little attention has been given to flavonoids, one type of polyphenols, which can be found in high levels mainly in fruits and vegetables, but also in other foods such as grains, cocoa, green tea or even in red wine. Flavonoids have anti-inflammatory, antioxidant and antiviral effects. Since it is known that diabetes induces oxidative stress and inflammation in the retina leading to neuronal death in the early stages of the disease, the use of these compounds can prove to be beneficial in the prevention or treatment of DR. In this review, we summarize the molecular and cellular effects of flavonoids in the diabetic retina. Full article

(This article belongs to the Special Issue Nutrition for Eye Health)

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33 pages, 547 KiB

Open AccessReview

Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma

by Annagrazia Adornetto, Laura Rombolà, Luigi Antonio Morrone, Carlo Nucci, Maria Tiziana Corasaniti, Giacinto Bagetta and Rossella Russo

Nutrients 2020, 12(10), 3158; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12103158 - 16 Oct 2020

Cited by 34 | Viewed by 6230

Abstract

Glaucoma, a leading cause of irreversible blindness worldwide, is an optic neuropathy characterized by the progressive death of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) is recognized as the main risk factor. Despite effective IOP-lowering therapies, the disease progresses in a significant number of patients. Therefore, alternative IOP-independent strategies aiming at halting or delaying RGC degeneration is the current therapeutic challenge for glaucoma management. Here, we review the literature on the neuroprotective activities, and the underlying mechanisms, of natural compounds and dietary supplements in experimental and clinical glaucoma. Full article

(This article belongs to the Special Issue Nutrition for Eye Health)

21 pages, 334 KiB

Open AccessReview

Potential Therapeutic Benefit of NAD⁺ Supplementation for Glaucoma and Age-Related Macular Degeneration

by Gloria Cimaglia, Marcela Votruba, James E. Morgan, Helder André and Pete A. Williams

Nutrients 2020, 12(9), 2871; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12092871 - 19 Sep 2020

Cited by 19 | Viewed by 6767

Abstract

Glaucoma and age-related macular degeneration are leading causes of irreversible blindness worldwide with significant health and societal burdens. To date, no clinical cures are available and treatments target only the manageable symptoms and risk factors (but do not remediate the underlying pathology of the disease). Both diseases are neurodegenerative in their pathology of the retina and as such many of the events that trigger cell dysfunction, degeneration, and eventual loss are due to mitochondrial dysfunction, inflammation, and oxidative stress. Here, we critically review how a decreased bioavailability of nicotinamide adenine dinucleotide (NAD; a crucial metabolite in healthy and disease states) may underpin many of these aberrant mechanisms. We propose how exogenous sources of NAD may become a therapeutic standard for the treatment of these conditions. Full article

(This article belongs to the Special Issue Nutrition for Eye Health)

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19 pages, 886 KiB

Open AccessReview

Dietary Patterns, Carbohydrates, and Age-Related Eye Diseases

by Sarah G. Francisco, Kelsey M. Smith, Gemma Aragonès, Elizabeth A. Whitcomb, Jasper Weinberg, Xuedi Wang, Eloy Bejarano, Allen Taylor and Sheldon Rowan

Nutrients 2020, 12(9), 2862; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12092862 - 18 Sep 2020

Cited by 30 | Viewed by 8648

Abstract

Over a third of older adults in the U.S. experience significant vision loss, which decreases independence and is a biomarker of decreased health span. As the global aging population is expanding, it is imperative to uncover strategies to increase health span and reduce the economic burden of this age-related disease. While there are some treatments available for age-related vision loss, such as surgical removal of cataracts, many causes of vision loss, such as dry age-related macular degeneration (AMD), remain poorly understood and no treatments are currently available. Therefore, it is necessary to better understand the factors that contribute to disease progression for age-related vision loss and to uncover methods for disease prevention. One such factor is the effect of diet on ocular diseases. There are many reviews regarding micronutrients and their effect on eye health. Here, we discuss the impact of dietary patterns on the incidence and progression of age-related eye diseases, namely AMD, cataracts, diabetic retinopathy, and glaucoma. Then, we focus on the specific role of dietary carbohydrates, first by outlining the physiological effects of carbohydrates on the body and then how these changes translate into eye and age-related ocular diseases. Finally, we discuss future directions of nutrition research as it relates to aging and vision loss, with a discussion of caloric restriction, intermittent fasting, drug interventions, and emerging randomized clinical trials. This is a rich field with the capacity to improve life quality for millions of people so they may live with clear vision for longer and avoid the high cost of vision-saving surgeries. Full article

(This article belongs to the Special Issue Nutrition for Eye Health)

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12 pages, 1057 KiB

Open AccessReview

Nutritional Optic Neuropathies: State of the Art and Emerging Evidences

by Matilde Roda, Natalie di Geronimo, Marco Pellegrini and Costantino Schiavi

Nutrients 2020, 12(9), 2653; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12092653 - 31 Aug 2020

Cited by 22 | Viewed by 5265

Abstract

Nutritional optic neuropathy is a cause of bilateral, symmetrical, and progressive visual impairment with loss of central visual acuity and contrast sensitivity, dyschromatopsia, and a central or centrocecal scotoma. The clinical features are not pathognomonic, since hereditary and toxic forms share similar signs and symptoms. It is becoming increasingly common due to the widespread of bariatric surgery and strict vegetarian or vegan diets, so even the scientific interest has recently increased. In particular, recent studies have focused on possible pathogenetic mechanisms, and on novel diagnostic and therapeutic strategies in order to prevent the onset, make a prompt diagnosis and an accurate nutritional supplementation, and to avoid irreversible optic nerve atrophy. Nowadays, there is clear evidence of the role of cobalamin, folic acid, thiamine, and copper, whereas further studies are needed to define the role of niacin, riboflavin, and pyridoxine. This review aims to summarize the etiology, diagnosis, and treatment of nutritional optic neuropathy, and it is addressed not only to ophthalmologists, but to all physicians who could come in contact with a patient with a possible nutritional optic neuropathy, being a fundamental multidisciplinary approach. Full article

(This article belongs to the Special Issue Nutrition for Eye Health)

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23 pages, 1106 KiB

Open AccessFeature PaperReview

Mitochondrial Dysfunction as a Novel Target for Neuroprotective Nutraceuticals in Ocular Diseases

by Chun-Ping Huang, Yi-Wen Lin, Yu-Chuen Huang and Fuu-Jen Tsai

Nutrients 2020, 12(7), 1950; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12071950 - 30 Jun 2020

Cited by 7 | Viewed by 3444

Abstract

The eyes require a rich oxygen and nutrient supply; hence, the high-energy demand of the visual system makes it sensitive to oxidative stress. Excessive free radicals result in mitochondrial dysfunction and lead to retinal neurodegeneration, as an early stage of retinal metabolic disorders. Retinal cells are vulnerable because of their coordinated interaction and intricate neural networks. Nutraceuticals are believed to target multiple pathways and have shown neuroprotective benefits by scavenging free radicals and promoting mitochondrial gene expression. Furthermore, encouraging results demonstrate that nutraceuticals improve the organization of retinal cells and visual functions. This review discusses the mitochondrial impairments of retinal cells and the mechanisms underlying the neuroprotective effects of nutraceuticals. However, some unsolved problems still exist between laboratory study and clinical therapy. Poor bioavailability and bioaccessibility strongly limit their development. A new delivery system and improved formulation may offer promise for health care applications. Full article

(This article belongs to the Special Issue Nutrition for Eye Health)

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16 pages, 651 KiB

Open AccessReview

The Role of Nutrition and Nutritional Supplements in Ocular Surface Diseases

by Marco Pellegrini, Carlotta Senni, Federico Bernabei, Arrigo F. G. Cicero, Aldo Vagge, Antonio Maestri, Vincenzo Scorcia and Giuseppe Giannaccare

Nutrients 2020, 12(4), 952; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12040952 - 30 Mar 2020

Cited by 45 | Viewed by 13007

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. Full article

(This article belongs to the Special Issue Nutrition for Eye Health)

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18 pages, 847 KiB

Open AccessReview

Diet-Induced Rodent Models of Diabetic Peripheral Neuropathy, Retinopathy and Nephropathy

by Inês Preguiça, André Alves, Sara Nunes, Pedro Gomes, Rosa Fernandes, Sofia D. Viana and Flávio Reis

Nutrients 2020, 12(1), 250; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12010250 - 18 Jan 2020

Cited by 38 | Viewed by 7861

Abstract

Unhealthy dietary habits are major modifiable risk factors for the development of type 2 diabetes mellitus, a metabolic disease with increasing prevalence and serious consequences. Microvascular complications of diabetes, namely diabetic peripheral neuropathy (DPN), retinopathy (DR), and nephropathy (DN), are associated with high morbidity rates and a heavy social and economic burden. Currently, available therapeutic options to counter the evolution of diabetic microvascular complications are clearly insufficient, which strongly recommends further research. Animal models are essential tools to dissect the molecular mechanisms underlying disease progression, to unravel new therapeutic targets, as well as to evaluate the efficacy of new drugs and/or novel therapeutic approaches. However, choosing the best animal model is challenging due to the large number of factors that need to be considered. This is particularly relevant for models induced by dietary modifications, which vary markedly in terms of macronutrient composition. In this article, we revisit the rodent models of diet-induced DPN, DR, and DN, critically comparing the main features of these microvascular complications in humans and the criteria for their diagnosis with the parameters that have been used in preclinical research using rodent models, considering the possible need for factors which can accelerate or aggravate these conditions. Full article

(This article belongs to the Special Issue Nutrition for Eye Health)

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