Special Issue "Nutrition for Eye Health"

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).

Special Issue Editor

Prof. Dr. Paola Bagnoli
E-Mail Website
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
Special Issues and Collections in MDPI journals

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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Article
Retinal Neurodegeneration: Correlation between Nutraceutical Treatment and Animal Model
Nutrients 2021, 13(3), 770; https://doi.org/10.3390/nu13030770 - 27 Feb 2021
Viewed by 624
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 [...] Read more.
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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Article
A Multi-Omics Approach Identifies Key Regulatory Pathways Induced by Long-Term Zinc Supplementation in Human Primary Retinal Pigment Epithelium
Nutrients 2020, 12(10), 3051; https://doi.org/10.3390/nu12103051 - 06 Oct 2020
Cited by 1 | Viewed by 927
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 [...] Read more.
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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Article
A Dietary Combination of Forskolin with Homotaurine, Spearmint and B Vitamins Protects Injured Retinal Ganglion Cells in a Rodent Model of Hypertensive Glaucoma
Nutrients 2020, 12(4), 1189; https://doi.org/10.3390/nu12041189 - 23 Apr 2020
Cited by 6 | Viewed by 1211
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 [...] Read more.
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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Article
The Use of Vitamins and Coenzyme Q10 for the Treatment of Vascular Occlusion Diseases Affecting the Retina
Nutrients 2020, 12(3), 723; https://doi.org/10.3390/nu12030723 - 09 Mar 2020
Cited by 2 | Viewed by 1957
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. [...] Read more.
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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Article
Maternal Lutein and Zeaxanthin Concentrations in Relation to Offspring Visual Acuity at 3 Years of Age: The GUSTO Study
Nutrients 2020, 12(2), 274; https://doi.org/10.3390/nu12020274 - 21 Jan 2020
Cited by 1 | Viewed by 1598
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 [...] Read more.
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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Article
Estimation of the Minimum Effective Dose of Dietary Supplement Crocetin for Prevention of Myopia Progression in Mice
Nutrients 2020, 12(1), 180; https://doi.org/10.3390/nu12010180 - 09 Jan 2020
Cited by 1 | Viewed by 1287
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 [...] Read more.
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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Review
The Benefits of Flavonoids in Diabetic Retinopathy
Nutrients 2020, 12(10), 3169; https://doi.org/10.3390/nu12103169 - 16 Oct 2020
Cited by 4 | Viewed by 1323
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% [...] Read more.
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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Review
Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma
Nutrients 2020, 12(10), 3158; https://doi.org/10.3390/nu12103158 - 16 Oct 2020
Cited by 3 | Viewed by 1063
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 [...] Read more.
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)
Review
Potential Therapeutic Benefit of NAD+ Supplementation for Glaucoma and Age-Related Macular Degeneration
Nutrients 2020, 12(9), 2871; https://doi.org/10.3390/nu12092871 - 19 Sep 2020
Cited by 2 | Viewed by 1835
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 [...] Read more.
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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Review
Dietary Patterns, Carbohydrates, and Age-Related Eye Diseases
Nutrients 2020, 12(9), 2862; https://doi.org/10.3390/nu12092862 - 18 Sep 2020
Cited by 2 | Viewed by 1768
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 [...] Read more.
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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Review
Nutritional Optic Neuropathies: State of the Art and Emerging Evidences
Nutrients 2020, 12(9), 2653; https://doi.org/10.3390/nu12092653 - 31 Aug 2020
Cited by 2 | Viewed by 1194
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 [...] Read more.
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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Review
Mitochondrial Dysfunction as a Novel Target for Neuroprotective Nutraceuticals in Ocular Diseases
Nutrients 2020, 12(7), 1950; https://doi.org/10.3390/nu12071950 - 30 Jun 2020
Viewed by 1053
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. [...] Read more.
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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Review
The Role of Nutrition and Nutritional Supplements in Ocular Surface Diseases
Nutrients 2020, 12(4), 952; https://doi.org/10.3390/nu12040952 - 30 Mar 2020
Cited by 8 | Viewed by 2695
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 [...] Read more.
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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Review
Diet-Induced Rodent Models of Diabetic Peripheral Neuropathy, Retinopathy and Nephropathy
Nutrients 2020, 12(1), 250; https://doi.org/10.3390/nu12010250 - 18 Jan 2020
Cited by 12 | Viewed by 1913
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 [...] Read more.
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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