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Bioactive Compounds in the Pathogenesis, Prevention, and Therapy of Eye Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 27027

Special Issue Editors

Prof. Dr. Janusz Blasiak

E-Mail Website
Guest Editor
Faculty of Biology and Environmental Sciences, Department of Molecular Genetics, University of Lodz, 90-136 Lodz, Poland
Interests: DNA and RNA structure; DNA damage and repair; DNA damage response; mutagenesis; cancer transformation; age-related macular degeneration; autophagy; mitochondrial quality control; mitophagy; miRNA-lncRNA regulation; gene regulation; epigenetics
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Kai Kaarniranta

E-Mail Website
Co-Guest Editor
Department of Ophthalmology, Kuopio University Hospital, 70211 Kuopio, Finland
Interests: aging; autophagy; eye diseases; genetics; macula; oxidative stress; proteolysis; retinal pigment epithelium
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Bioactive compounds derived from natural products include a diverse class of compounds with different chemical structures comprising polyphenols, carotenoids, tocopherols, phytosterols, organosulfur compounds, and other classes. While many of them are not essential, their substantial proportion may modulate a number of processes ongoing in our body and are useful in the prevention and therapy of various human disorders. Although several bioactive compounds are reported to have a beneficial effect on vision, the results of clinical trials and systematic reviews on their efficacy in various eye diseases are not conclusive. Therefore, studies on the effects of bioactive compounds in eye diseases are needed and should primarily focus on the involvement of bioactive compounds in pathogenesis mechanisms and preventive and therapeutic potential.

This Special Issue welcomes both original papers and reviews addressing the potential of bioactive compounds in eye disease pathogenesis, prevention, and therapy. The following diseases may be addressed: refractive disorders, dry eye syndrome, cornea degenerations and dystrophies, conjunctiva disorders, cataracts, uveitis, glaucoma, age-related macular degeneration, diabetic retinopathy, albinism, retinopathy of prematurity, retinitis pigmentosa, ocular tumors, lysosomal storage diseases, and rare ophthalmic genetic diseases, as well as chemical and physical damage of the eye studied in cell cultures, animal models, or human material. The following keywords may be useful in selecting a paper topic.

Keywords (all in relation to bioactive compounds in eye diseases):

  • Pathogenesis, prevention, and therapy
  • Bioavailability
  • Genetic/epigenetic
  • Oxidative stress and antioxidant system
  • Stress response
  • Molecular chaperones
  • Senescence and organismal aging
  • Mitochondrial quality control
  • Autophagy and mitophagy
  • DNA damage reaction in the nucleus and mitochondria
  • DNA damage and repair
  • Mutations/polymorphisms of genes
  • Programmed cell death, including apoptosis, pyroptosis, and necroptosis
  • Inflammation and the inflammasome activation
  • miRNA-lncRNA regulation

Prof. Dr. Janusz Blasiak
Prof. Dr. Kai Kai Kaarniranta
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Related Special Issue

Published Papers (6 papers)

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Research

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16 pages, 2465 KiB  
Article
Protective Effects of a Lutein Ester Prodrug, Lutein Diglutaric Acid, against H2O2-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells
by Chawanphat Muangnoi, Rianthong Phumsuay, Nattapong Jongjitphisut, Pasin Waikasikorn, Monsin Sangsawat, Paitoon Rashatasakhon, Luminita Paraoan and Pornchai Rojsitthisak
Int. J. Mol. Sci. 2021, 22(9), 4722; https://doi.org/10.3390/ijms22094722 - 29 Apr 2021
Cited by 26 | Viewed by 3614
Abstract
Oxidative stress-induced cell damage and death of the retinal pigmented epithelium (RPE), a polarized monolayer that maintains retinal health and homeostasis, lead to the development of age-related macular degeneration (AMD). Several studies show that the naturally occurring antioxidant Lutein (Lut) can protect RPE [...] Read more.
Oxidative stress-induced cell damage and death of the retinal pigmented epithelium (RPE), a polarized monolayer that maintains retinal health and homeostasis, lead to the development of age-related macular degeneration (AMD). Several studies show that the naturally occurring antioxidant Lutein (Lut) can protect RPE cells from oxidative stress. However, the poor solubility and low oral bioavailability limit the potential of Lut as a therapeutic agent. In this study, lutein diglutaric acid (Lut-DG), a prodrug of Lut, was synthesized and its ability to protect human ARPE-19 cells from oxidative stress was tested compared to Lut. Both Lut and Lut-DG significantly decreased H2O2-induced reactive oxygen species (ROS) production and protected RPE cells from oxidative stress-induced death. Moreover, the immunoblotting analysis indicated that both drugs exerted their protective effects by modulating phosphorylated MAPKs (p38, ERK1/2 and SAPK/JNK) and downstream molecules Bax, Bcl-2 and Cytochrome c. In addition, the enzymatic antioxidants glutathione peroxidase (GPx) and catalase (CAT) and non-enzymatic antioxidant glutathione (GSH) were enhanced in cells treated with Lut and Lut-DG. In all cases, Lut-DG was more effective than its parent drug against oxidative stress-induced damage to RPE cells. These findings highlight Lut-DG as a more potent compound than Lut with the protective effects against oxidative stress in RPE cells through the modulation of key MAPKs, apoptotic and antioxidant molecular pathways. Full article
(This article belongs to the Special Issue Bioactive Compounds in the Pathogenesis, Prevention, and Therapy of Eye Diseases)
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18 pages, 3034 KiB  
Article
Lactobacillus paracasei KW3110 Suppresses Inflammatory Stress-Induced Premature Cellular Senescence of Human Retinal Pigment Epithelium Cells and Reduces Ocular Disorders in Healthy Humans
by Takahiro Yamazaki, Hiroaki Suzuki, Sayuri Yamada, Konomi Ohshio, Miho Sugamata, Takahiro Yamada and Yuji Morita
Int. J. Mol. Sci. 2020, 21(14), 5091; https://doi.org/10.3390/ijms21145091 - 18 Jul 2020
Cited by 9 | Viewed by 4561
Abstract
Lactobacillus paracasei KW3110 (KW3110) has anti-inflammatory effects and mitigates retinal pigment epithelium (RPE) cell damage caused by blue-light exposure. We investigated whether KW3110 suppresses chronic inflammatory stress-induced RPE cell damage by modulating immune cell activity and whether it improves ocular disorders in healthy [...] Read more.
Lactobacillus paracasei KW3110 (KW3110) has anti-inflammatory effects and mitigates retinal pigment epithelium (RPE) cell damage caused by blue-light exposure. We investigated whether KW3110 suppresses chronic inflammatory stress-induced RPE cell damage by modulating immune cell activity and whether it improves ocular disorders in healthy humans. First, we showed that KW3110 treatment of mouse macrophages (J774A.1) produced significantly higher levels of interleukin-10 as compared with other lactic acid bacterium strains (all p < 0.01). Transferring supernatant from KW3110- and E. coli 0111:B4 strain and adenosine 5′-triphosphate (LPS/ATP)-stimulated J774A.1 cells to human retinal pigment epithelium (ARPE-19) cells suppressed senescence-associated phenotypes, including proliferation arrest, abnormal appearance, cell cycle arrest, and upregulation of cytokines, and also suppressed expression of tight junction molecule claudin-1. A randomized, double-blind, placebo-controlled parallel-group study of healthy subjects (n = 88; 35 to below 50 years) ingesting placebo or KW3110-containing supplements for 8 weeks showed that changes in critical flicker frequency, an indicator of eye fatigue, from the week-0 value were significantly larger in the KW3110 group at weeks 4 (p = 0.040) and 8 (p = 0.036). These results suggest that KW3110 protects ARPE-19 cells against premature senescence and aberrant expression of tight junction molecules caused by chronic inflammatory stress, and may improve chronic eye disorders including eye fatigue. Full article
(This article belongs to the Special Issue Bioactive Compounds in the Pathogenesis, Prevention, and Therapy of Eye Diseases)
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19 pages, 2908 KiB  
Article
Effect of Berberine on Glycation, Aldose Reductase Activity, and Oxidative Stress in the Lenses of Streptozotocin-Induced Diabetic Rats In Vivo—A Preliminary Study
by Maria Zych, Weronika Wojnar, Magdalena Kielanowska, Joanna Folwarczna and Ilona Kaczmarczyk-Sedlak
Int. J. Mol. Sci. 2020, 21(12), 4278; https://doi.org/10.3390/ijms21124278 - 16 Jun 2020
Cited by 20 | Viewed by 4295
Abstract
Diabetes mellitus affects the eye lens, leading to cataract formation by glycation, osmotic stress, and oxidative stress. Berberine, an isoquinoline alkaloid, is a natural compound that has been reported to counteract all these pathological processes in various tissues and organs. The goal of [...] Read more.
Diabetes mellitus affects the eye lens, leading to cataract formation by glycation, osmotic stress, and oxidative stress. Berberine, an isoquinoline alkaloid, is a natural compound that has been reported to counteract all these pathological processes in various tissues and organs. The goal of this study was to evaluate whether berberine administered at a dose of 50 mg/kg by oral gavage for 28 days to rats with streptozotocin-induced diabetes reveals such effects on the biochemical parameters in the lenses. For this purpose, the following lenticular parameters were studied: concentrations of soluble protein, non-protein sulfhydryl groups (NPSH), advanced oxidation protein products (AOPP), advanced glycation end-products (AGEs), thiobarbituric acid reactive substances (TBARS), and activities of aldose reductase (AR), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Diabetes induced unfavorable changes in the majority of the examined parameters. The administration of berberine resulted in an increased soluble protein level, decreased activity of AR, and lowered AOPP and AGEs levels. The results suggest that berberine administered orally positively affects the lenses of diabetic rats, and should be further examined with regard to its anticataract potential. Full article
(This article belongs to the Special Issue Bioactive Compounds in the Pathogenesis, Prevention, and Therapy of Eye Diseases)
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15 pages, 18709 KiB  
Article
Epigallocatechin 3-Gallate Has a Neuroprotective Effect in Retinas of Rabbits with Ischemia/Reperfusion through the Activation of Nrf2/HO-1
by Josué Rivera-Pérez, Martín Martínez-Rosas, César A. Conde-Castañón, Julia D. Toscano-Garibay, Nancy J. Ruiz-Pérez, Pedro L. Flores, Elvia Mera Jiménez and Javier Flores-Estrada
Int. J. Mol. Sci. 2020, 21(10), 3716; https://doi.org/10.3390/ijms21103716 - 25 May 2020
Cited by 21 | Viewed by 3823
Abstract
Retinal ischemia-reperfusion (rI/R) generates an oxidative condition causing the death of neuronal cells. Epigallocatechin 3-gallate (EGCG) has antioxidant and anti-inflammatory properties. Nonetheless, its correlation with the pathway of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) for the protection of the retina is [...] Read more.
Retinal ischemia-reperfusion (rI/R) generates an oxidative condition causing the death of neuronal cells. Epigallocatechin 3-gallate (EGCG) has antioxidant and anti-inflammatory properties. Nonetheless, its correlation with the pathway of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) for the protection of the retina is unknown. We aimed to evaluate the neuroprotective efficacy of single-doses of EGCG in rI/R and its association with Nrf2/Ho-1 expression. In albino rabbits, rI/R was induced and single-doses of EGCG in saline (0–30 mg/kg) were intravenously administered to select an optimal EGCG concentration that protects from retina damage. To reach this goal, retinal structural changes, gliosis by glial fibrillary acidic protein (GFAP) immunostaining, and lipid peroxidation level by TBARS (thiobarbituric acid reactive substance) assay were determined. EGCG in a dose of 15 mg/kg (E15) presented the lowest levels of histological damage, gliosis, and oxidative stress in the studied groups. To determine the neuroprotective efficacy of E15 in a timeline (6, 24, and 48 h after rI/R), and its association with the Nrf2/HO-1 pathway, the following assays were done by immunofluorescence: apoptosis (TUNEL assay), necrosis (high-mobility group box-1; HMGB1), Nrf2, and HO-1. In addition, the Ho-1 mRNA (qPCR) and lipid peroxidation levels were evaluated. E15 showed a protective effect during the first 6 h, compared to 24 and 48 h after rI/R, as revealed by a decrease in the levels of all damage markers. Nuclear translocation Nrf2 and HO-1 staining were increased, including Ho-1 mRNA levels. In conclusion, a single dose of E15 decreases the death of neuronal cells induced by oxidative stress during the first 6 h after rI/R. This protective effect is associated with the nuclear translocation of Nrf2 and with an elevation of Ho-1 expression. Full article
(This article belongs to the Special Issue Bioactive Compounds in the Pathogenesis, Prevention, and Therapy of Eye Diseases)
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Review

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29 pages, 3795 KiB  
Review
New Highlights of Resveratrol: A Review of Properties against Ocular Diseases
by Dominique Delmas, Clarisse Cornebise, Flavie Courtaut, Jianbo Xiao and Virginie Aires
Int. J. Mol. Sci. 2021, 22(3), 1295; https://doi.org/10.3390/ijms22031295 - 28 Jan 2021
Cited by 51 | Viewed by 6334
Abstract
Eye diseases are currently a major public health concern due to the growing number of cases resulting from both an aging of populations and exogenous factors linked to our lifestyles. Thus, many treatments including surgical pharmacological approaches have emerged, and special attention has [...] Read more.
Eye diseases are currently a major public health concern due to the growing number of cases resulting from both an aging of populations and exogenous factors linked to our lifestyles. Thus, many treatments including surgical pharmacological approaches have emerged, and special attention has been paid to prevention, where diet plays a preponderant role. Recently, potential antioxidants such as resveratrol have received much attention as potential tools against various ocular diseases. In this review, we focus on the mechanisms of resveratrol against ocular diseases, in particular age-related macular degeneration, glaucoma, cataract, diabetic retinopathy, and vitreoretinopathy. We analyze, in relation to the different steps of each disease, the resveratrol properties at multiple levels, such as cellular and molecular signaling as well as physiological effects. We show and discuss the relationship to reactive oxygen species, the regulation of inflammatory process, and how resveratrol can prevent ocular diseases through a potential epigenetic action by the activation of sirtuin-1. Lastly, various new forms of resveratrol delivery are emerging at the same time as some clinical trials are raising more questions about the future of resveratrol as a potential tool for prevention or in therapeutic strategies against ocular diseases. More preclinical studies are required to provide further insights into RSV’s potential adjuvant activity. Full article
(This article belongs to the Special Issue Bioactive Compounds in the Pathogenesis, Prevention, and Therapy of Eye Diseases)
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19 pages, 1797 KiB  
Review
Fucoidans as Potential Therapeutics for Age-Related Macular Degeneration—Current Evidence from In Vitro Research
by Philipp Dörschmann and Alexa Klettner
Int. J. Mol. Sci. 2020, 21(23), 9272; https://doi.org/10.3390/ijms21239272 - 4 Dec 2020
Cited by 20 | Viewed by 3430
Abstract
Age-related macular degeneration (AMD) is the major reason for blindness in the industrialized world with limited treatment options. Important pathogenic pathways in AMD include oxidative stress and vascular endothelial growth factor (VEGF) secretion. Due to their bioactivities, fucoidans have recently been suggested as [...] Read more.
Age-related macular degeneration (AMD) is the major reason for blindness in the industrialized world with limited treatment options. Important pathogenic pathways in AMD include oxidative stress and vascular endothelial growth factor (VEGF) secretion. Due to their bioactivities, fucoidans have recently been suggested as potential therapeutics. This review gives an overview of the recent developments in this field. Recent studies have characterized several fucoidans from different species, with different molecular characteristics and different extraction methods, in regard to their ability to reduce oxidative stress and inhibit VEGF in AMD-relevant in vitro systems. As shown in these studies, fucoidans exhibit a species dependency in their bioactivity. Additionally, molecular properties such as molecular weight and fucose content are important issues. Fucoidans from Saccharina latissima and Laminaria hyperborea were identified as the most promising candidates for further development. Further research is warranted to establish fucoidans as potential therapeutics for AMD. Full article
(This article belongs to the Special Issue Bioactive Compounds in the Pathogenesis, Prevention, and Therapy of Eye Diseases)
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