Eye Diseases: From Cellular and Molecular Mechanisms to Novel Therapeutic Approaches

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (1 June 2021) | Viewed by 21874

Special Issue Editor

Kanazawa Medical University, Kahoku District, Ishikawa, Japan
Interests: cataract; posterior capsular opacification; oxidative stress; epithelial-to mesenchymal transition; antioxidant; antiglycation

Special Issue Information

Dear Colleagues,

This Special Issue, “Eye Diseases: From Cellular and Molecular Mechanisms to Novel Therapeutic Approaches”, will cover a selection of recent research topics and current review articles related to the ocular pathological molecular mechanisms and management of eye disease. It will include papers investigating experimental and clinical studies examining potential treatments or preventive measures to attenuate eye disease. Up-to-date review articles, commentaries, and experimental papers are all welcome.

We look forward to your contributions to this Special Issue.

Dr. Eri Kubo
Guest Editor

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Keywords

  • cataract
  • posterior capsular opacification
  • oxidative stress
  • epithelial-to-mesenchymal transition
  • antioxidant
  • antiglycation

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Published Papers (6 papers)

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Research

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18 pages, 16842 KiB  
Article
Role of Decorin in Posterior Capsule Opacification and Eye Lens Development
by Shinsuke Shibata, Naoko Shibata, Satoshi Ohtsuka, Yasuo Yoshitomi, Etsuko Kiyokawa, Hideto Yonekura, Dhirendra P. Singh, Hiroshi Sasaki and Eri Kubo
Cells 2021, 10(4), 863; https://doi.org/10.3390/cells10040863 - 9 Apr 2021
Cited by 7 | Viewed by 3289
Abstract
Decorin (DCN) is involved in a variety of physiological and pathological processes. Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) has been proposed as a major cause for the development of posterior capsule opacification (PCO) after cataract surgery. We investigated the plausible target [...] Read more.
Decorin (DCN) is involved in a variety of physiological and pathological processes. Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) has been proposed as a major cause for the development of posterior capsule opacification (PCO) after cataract surgery. We investigated the plausible target gene(s) that suppress PCO. The expression of Dcn was significantly upregulated in rat PCO tissues compared to that observed in the control using a microarray-based approach. LECs treated with fibroblast growth factor (FGF) 2 displayed an enhanced level of DCN expression, while LECs treated with transforming growth factor (TGF)β-2 showed a decrease in DCN expression. The expression of tropomyosin 1 (Tpm1), a marker of lens EMT increased after the addition of TGFβ-2 in human LEC; however, upregulation of Tpm1 mRNA or protein expression was reduced in human LECs overexpressing human DCN (hDCN). No phenotypic changes were observed in the lenses of 8- and 48-week-old transgenic mice for lens-specific hDCN (hDCN-Tg). Injury-induced EMT of the mouse lens, and the expression patterns of α smooth muscle actin, were attenuated in hDCN-Tg mice lenses. Overexpression of DCN inhibited the TGFβ-2-induced upregulation of Tpm1 and EMT observed during wound healing of the lens, but it did not affect mouse lens morphology until 48 weeks of age. Our findings demonstrate that DCN plays a significant role in regulating EMT formation of LECs and PCO, and suggest that for therapeutic intervention, maintenance of physiological expression of DCN is essential to attenuate EMT progression and PCO formation. Full article
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20 pages, 4843 KiB  
Article
Novel Technique for Retinal Nerve Cell Regeneration with Electrophysiological Functions Using Human Iris-Derived iPS Cells
by Naoki Yamamoto, Noriko Hiramatsu, Mahito Ohkuma, Natsuko Hatsusaka, Shun Takeda, Noriaki Nagai, Ei-ichi Miyachi, Masashi Kondo, Kazuyoshi Imaizumi, Masayuki Horiguchi, Eri Kubo and Hiroshi Sasaki
Cells 2021, 10(4), 743; https://doi.org/10.3390/cells10040743 - 28 Mar 2021
Cited by 5 | Viewed by 3334
Abstract
Regenerative medicine in ophthalmology that uses induced pluripotent stem cells (iPS) cells has been described, but those studies used iPS cells derived from fibroblasts. Here, we generated iPS cells derived from iris cells that develop from the same inner layer of the optic [...] Read more.
Regenerative medicine in ophthalmology that uses induced pluripotent stem cells (iPS) cells has been described, but those studies used iPS cells derived from fibroblasts. Here, we generated iPS cells derived from iris cells that develop from the same inner layer of the optic cup as the retina, to regenerate retinal nerves. We first identified cells positive for p75NTR, a marker of retinal tissue stem and progenitor cells, in human iris tissue. We then reprogrammed the cultured p75NTR-positive iris tissue stem/progenitor (H-iris stem/progenitor) cells to create iris-derived iPS (H-iris iPS) cells for the first time. These cells were positive for iPS cell markers and showed pluripotency to differentiate into three germ layers. When H-iris iPS cells were pre-differentiated into neural stem/progenitor cells, not all cells became positive for neural stem/progenitor and nerve cell markers. When these cells were pre-differentiated into neural stem/progenitor cells, sorted with p75NTR, and used as a medium for differentiating into retinal nerve cells, the cells differentiated into Recoverin-positive cells with electrophysiological functions. In a different medium, H-iris iPS cells differentiated into retinal ganglion cell marker-positive cells with electrophysiological functions. This is the first demonstration of H-iris iPS cells differentiating into retinal neurons that function physiologically as neurons. Full article
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17 pages, 4312 KiB  
Article
Regulation of Endothelium-Reticulum-Stress-Mediated Apoptotic Cell Death by a Polymethoxylated Flavone, Nobiletin, Through the Inhibition of Nuclear Translocation of Glyceraldehyde 3-Phosphate Dehydrogenase in Retinal Müller Cells
by Yoshiki Miyata, Kazuya Matsumoto, Shuichi Kusano, Yoshio Kusakabe, Yoshiya Katsura, Tetsuta Oshitari and Hiroshi Kosano
Cells 2021, 10(3), 669; https://doi.org/10.3390/cells10030669 - 17 Mar 2021
Cited by 8 | Viewed by 2395
Abstract
In the early stages of diabetic retinopathy (DR), subtle biochemical and functional alterations occur in Müller cells, which are one of the components of the blood–retinal barrier (BRB). Müller cells are the principal glia of the retina and have shown a strong involvement [...] Read more.
In the early stages of diabetic retinopathy (DR), subtle biochemical and functional alterations occur in Müller cells, which are one of the components of the blood–retinal barrier (BRB). Müller cells are the principal glia of the retina and have shown a strong involvement in the maintenance of homeostasis and the development of retinal tissue. Their functional abnormalities and eventual loss have been correlated with a decrease in the tight junctions between endothelial cells and a consequent breakdown of the BRB, leading to the development of DR. We demonstrated that the endothelium reticulum (ER) triggers Müller cell death and that nuclear accumulation of glyceraldehyde 3-phosphate dehydrogenase is closely associated with ER-induced Müller cell death. In addition, induction of ER stress in Müller cells increased vascular endothelial growth factor expression but decreased pigment-epithelium-derived factor (PEDF) expression in Müller cells. We found that nobiletin, a polymethoxylated flavone from citrus explants, exerts protective action against ER-stress-induced Müller cell death. In addition, nobiletin was found to augment PEDF expression in Müller cells, which may lead to the protection of BRB integrity. These results suggest that nobiletin can be an attractive candidate for the protection of the BRB from breakdown in DR. Full article
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11 pages, 2710 KiB  
Article
Effect of Alpha-Glucosyl-Hesperidin Consumption on Lens Sclerosis and Presbyopia
by Yosuke Nakazawa, Yuri Doki, Yuki Sugiyama, Ryota Kobayashi, Noriaki Nagai, Naoki Morisita, Shin Endo, Megumi Funakoshi-Tago and Hiroomi Tamura
Cells 2021, 10(2), 382; https://doi.org/10.3390/cells10020382 - 12 Feb 2021
Cited by 8 | Viewed by 3029
Abstract
Presbyopia is characterized by a decline in the ability to accommodate the lens. The most commonly accepted theory for the onset of presbyopia is an age-related increase in the stiffness of the lens. However, the cause of lens sclerosis remains unclear. With age, [...] Read more.
Presbyopia is characterized by a decline in the ability to accommodate the lens. The most commonly accepted theory for the onset of presbyopia is an age-related increase in the stiffness of the lens. However, the cause of lens sclerosis remains unclear. With age, water microcirculation in the lens could change because of an increase in intracellular pressure. In the lens, the intracellular pressure is controlled by the Transient Receptor Potential Vanilloid (TRPV) 1 and TRPV4 feedback pathways. In this study, we tried to elucidate that administration of α-glucosyl-hesperidin (G-Hsd), previously reported to prevent nuclear cataract formation, affects lens elasticity and the distribution of TRPV channels and Aquaporin (AQP) channels to meet the requirement of intracellular pressure. As a result, the mouse control lens was significantly toughened compared to both the 1% and 2% G-Hsd mouse lens treatments. The anti-oxidant levels in the lens and plasma decreased with age; however, this decrease could be nullified with either 1% or 2% G-Hsd treatment in a concentration- and exposure time-dependent manner. Moreover, G-Hsd treatment affected the TRPV4 distribution, but not TRPV1, AQP0, and AQP5, in the peripheral area and could maintain intracellular pressure. These findings suggest that G-Hsd has great potential as a compound to prevent presbyopia and/or cataract formation. Full article
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15 pages, 2775 KiB  
Article
In Situ Gel Incorporating Disulfiram Nanoparticles Rescues the Retinal Dysfunction via ATP Collapse in Otsuka Long–Evans Tokushima Fatty Rats
by Saori Deguchi, Fumihiko Ogata, Mizuki Yamaguchi, Misa Minami, Hiroko Otake, Kazutaka Kanai, Naohito Kawasaki and Noriaki Nagai
Cells 2020, 9(10), 2171; https://doi.org/10.3390/cells9102171 - 25 Sep 2020
Cited by 11 | Viewed by 2586
Abstract
We attempted to design an ophthalmic in situ gel formulation incorporating disulfiram (DIS) nanoparticles (Dis-NPs/ISG) and demonstrated the therapeutic effect of Dis-NPs/ISG on retinal dysfunction in 15-month-old Otsuka Long–Evans Tokushima Fatty (OLETF) rats, a rat model of diabetes. The DIS particles were crushed [...] Read more.
We attempted to design an ophthalmic in situ gel formulation incorporating disulfiram (DIS) nanoparticles (Dis-NPs/ISG) and demonstrated the therapeutic effect of Dis-NPs/ISG on retinal dysfunction in 15-month-old Otsuka Long–Evans Tokushima Fatty (OLETF) rats, a rat model of diabetes. The DIS particles were crushed using a bead mill to prepare the nanoparticles, and the Dis-NPs/ISG was prepared using a combination of the DIS nanoparticles and an in situ gelling system based on methylcellulose (MC). The particle size of the Dis-NPs/ISG was 80–250 nm, and there was no detectable precipitation or aggregation for 1 month. Moreover, the Dis-NPs/ISG was gelled at 37 °C, and the drug was delivered into the retina by instillation. Only diethyldithiocarbamate (DDC) was detected in the retina (DIS was not detected) when the Dis-NPs/ISG was instilled in the right eye, and the DDC levels in the right retina were significantly higher than those in the left retina. In addition, the retinal residence time of the drug was prolonged by the application of the in situ gelling system, since the DDC levels in the retinas of rats instilled with Dis-NPs/ISG were higher than those in DIS nanoparticles without MC. Furthermore, repetitive instillation of the Dis-NPs/ISG attenuated the deterioration of electroretinograms (ERGs) in 15-month-old OLETF rats by preventing the collapse of ATP production via excessive nitric oxide and recovered the decrease in retinal function. These findings provide important information for the development of novel therapeutic approaches to diabetic retinopathy. Full article
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Review

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18 pages, 823 KiB  
Review
The Transmission of SARS-CoV-2 Infection on the Ocular Surface and Prevention Strategies
by Koji Kitazawa, Stefanie Deinhardt-Emmer, Takenori Inomata, Sharvari Deshpande and Chie Sotozono
Cells 2021, 10(4), 796; https://doi.org/10.3390/cells10040796 - 2 Apr 2021
Cited by 23 | Viewed by 6380
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health problem. Although the respiratory system is the main impaired organ, conjunctivitis is one of its common findings. However, it is not yet understood if SARS-CoV-2 can infect the eye and if [...] Read more.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health problem. Although the respiratory system is the main impaired organ, conjunctivitis is one of its common findings. However, it is not yet understood if SARS-CoV-2 can infect the eye and if the ocular surface can be a potential route of SARS-CoV-2 transmissions. Our review focuses on the viral entry mechanisms to give a better understanding of the interaction between SARS-CoV-2 and the eye. We highlighted findings that give evidence for multiple potential receptors of SARS-CoV-2 on the ocular surface. Additionally, we focused on data concerning the detection of viral RNA and its spike protein in the various ocular tissues from patients. However, the expression level seemed to be relatively low compared to the respiratory tissues as a result of a unique environment surrounding the ocular surface and the innate immune response of SARS-CoV-2. Nevertheless, our review suggests the ocular surface as a potential route for SARS-CoV-2 transmission, and as a result of this study we strongly recommend the protection of the eyes for ophthalmologists and patients at risk. Full article
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