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Ischemic Retinopathies: New Insights into Molecular Mechanisms and Therapeutic Approaches

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A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (10 September 2021) | Viewed by 11243

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Special Issue Editors

Dr. Menaka Thounaojam

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Guest Editor

Department of Ophthalmology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
Interests: miRNA; Retinopathy of prematurity; bile acid metabolism
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Manuela Bartoli

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Guest Editor

Department of Ophthalmology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
Interests: miRNA; retinopathy of prematurity; diabetic retinopathy; oxidative stress; senescence
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Retinal ischemia is a major cause of visual impairment and is related to various ocular diseases such as diabetic retinopathy, retinopathy of prematurity, retinal vascular occlusion, and acute glaucoma. Growing evidence shows that oxidative stress and inflammatory processes are significant contributors to the pathogenesis of ischemic retinopathies (IRs). In the ischemic retina, the overwhelming production of free radicals leads to neurodegeneration, inflammation, activation of glial cells, and vascular damage. Despite the beneficial effects of currently used therapies (photocoagulation and anti-VEGF therapy), there is a great need to identify novel targets to prevent these ocular pathologies. A better understanding of the molecular mechanisms associated with various IRs can lead to the identification of new therapeutic targets that allow the development of new therapeutic approaches.

The purpose of this Special Issue is to highlight recent advances in understanding the molecular mechanisms of IRs and to explore promising new biomolecules and therapeutic strategies for the treatment of IRs. This Special Issue welcomes submissions of original research, comprehensive reviews, and methods articles on various aspects of IRs.

Dr. Menaka Thounaojam
Dr. Manuela Bartoli
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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Diabetic retinopathy
Retinopathy of prematurity
Energy metabolism
Therapeutic targets
Oxidative stress
Inflammation
Biomolecules

Published Papers (4 papers)

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Research

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14 pages, 2246 KiB

Open AccessArticle

Effects of Hypoxic Preconditioning and Vascular Endothelial Growth Factor on the Survival of Isolated Primary Retinal Ganglion Cells

by Hyoung Won Bae, Wungrak Choi, Ah Reum Hwang, Sang Yeop Lee, Gong Je Seong and Chan Yun Kim

Biomolecules 2021, 11(3), 391; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11030391 - 06 Mar 2021

Cited by 2 | Viewed by 1614

Abstract

This study aimed to investigate the effect of hypoxic preconditioning (HPC) on primary retinal ganglion cell (RGC) survival and the associated mechanism, including the role of vascular endothelial growth factor (VEGF). Retinas were separated from the enucleated eyeballs of Sprague–Dawley rats on postnatal days 1–4. RGCs were harvested using an immunopanning-magnetic separation system and maintained for 24 h in a defined medium. Hypoxic damage (0.3% O₂) was inflicted on the cells using a CO₂ chamber. Anti-VEGF antibody (bevacizumab) was administered to RGCs exposed to hypoxic conditions, and RGC survival rate was compared to that of non-anti-VEGF antibody-treated RGCs. HPC lasting 4 h significantly increased RGC survival rate. In the RGCs exposed to hypoxic conditions for 4 h, VEGF mRNA and protein levels were significantly increased. Treatment with high dose bevacizumab (>1 mg/mL) countered HPC-mediated RGC survival. Protein kinase B and focal adhesion kinase levels were significantly increased in 4-h hypoxia-treated RGCs. HPC showed beneficial effects on primary RGC survival. However, only specifically controlled exposure to hypoxic conditions rendered neuroprotective effects. Strong inhibition of VEGF inhibited HPC-mediated RGC survival. These results indicate that VEGF may play an essential role in promoting cell survival under hypoxic conditions. Full article

(This article belongs to the Special Issue Ischemic Retinopathies: New Insights into Molecular Mechanisms and Therapeutic Approaches)

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16 pages, 5831 KiB

Open AccessArticle

Changes in the Systemic Expression of Sirtuin-1 and Oxidative Stress after Intravitreal Anti-Vascular Endothelial Growth Factor in Patients with Retinal Vein Occlusion

by De-Kuang Hwang, Yuh-Lih Chang, Tai-Chi Lin, Chi-Hsien Peng, Ke-Hung Chien, Ching-Yao Tsai, Shih-Jen Chen, Kuan-Hsuan Chen and Min-Yen Hsu

Biomolecules 2020, 10(10), 1414; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10101414 - 06 Oct 2020

Cited by 8 | Viewed by 2340

Abstract

Objectives: Retinal vein occlusions (RVO) are associated with systemic risk factors. However, the ocular occlusive events might also influence a patient’s systemic condition. This study tried to investigate serum biomarkers associated with oxidative stress, before and after intravitreal anti-vascular endothelial growth factor (aVEGF) therapy in patients with RVOs. Methods: Newly-onset RVO patients were categorized into two groups: comorbid with macular edema requiring aVEGF therapy (treatment group) and no edema (observation group). Age and sex-matched patients (who received cataract surgery) were included as the control group. Intravitreal ranibizumab with a pro-re-nata regimen were administered. Serum samples were collected prior to treatment, at 6 and 12 months after therapy/observation and were collected once before controls who received cataract surgery. mRNA expression of sirtuin-1, its downstream genes, anti-oxidative biomarkers, and proinflammatory cytokines were measured. Results: There were 32, 26, and 34 patients enrolled in the treatment, observation, and control groups, respectively. The expressions of sirtuin-1 and its downstream genes were significantly lower in patients with RVO compared with the control group. Sirtuin-1 gene expression increased after 1 year of aVEGF therapy in the treatment group but remained unchanged in the observation group. Biomarkers of oxidative stress and proinflammatory cytokines were reduced after 1 year of aVEGF therapy. These biomarkers remained with no changes in the observation group. Conclusions: Our study showed that the systemic oxidative stress increased in RVO patients. The aVEGF therapy could alter the gene expression of anti-oxidative proteins and reduce systemic oxidative stress in these patients. Full article

(This article belongs to the Special Issue Ischemic Retinopathies: New Insights into Molecular Mechanisms and Therapeutic Approaches)

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14 pages, 1862 KiB

Open AccessArticle

A Fairy Chemical Suppresses Retinal Angiogenesis as a HIF Inhibitor

by Deokho Lee, Yukihiro Miwa, Jing Wu, Chiho Shoda, Heonuk Jeong, Hirokazu Kawagishi, Kazuo Tsubota and Toshihide Kurihara

Biomolecules 2020, 10(10), 1405; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10101405 - 04 Oct 2020

Cited by 19 | Viewed by 3315

Abstract

Neovascular retinal degeneration is a leading cause of blindness in advanced countries. Anti-vascular endothelial growth factor (VEGF) drugs have been used for neovascular retinal diseases; however, anti-VEGF drugs may cause the development of chorioretinal atrophy in chronic therapy as they affect the physiological amount of VEGF needed for retinal homeostasis. Hypoxia-inducible factor (HIF) is a transcription factor inducing VEGF expression under hypoxic and other stress conditions. Previously, we demonstrated that HIF was involved with pathological retinal angiogenesis in murine models of oxygen-induced retinopathy (OIR), and pharmacological HIF inhibition prevented retinal neovascularization by reducing an ectopic amount of VEGF. Along with this, we attempted to find novel effective HIF inhibitors. Compounds originally isolated from mushroom-forming fungi were screened for prospective HIF inhibitors utilizing cell lines of 3T3, ARPE-19 and 661W. A murine OIR model was used to examine the anti-angiogenic effects of the compounds. As a result, 2-azahypoxanthine (AHX) showed an inhibitory effect on HIF activation and suppressed Vegf mRNA upregulation under CoCl₂-induced pseudo-hypoxic conditions. Oral administration of AHX significantly suppressed retinal neovascular tufts in the OIR model. These data suggest that AHX could be a promising anti-angiogenic agent in retinal neovascularization by inhibiting HIF activation. Full article

(This article belongs to the Special Issue Ischemic Retinopathies: New Insights into Molecular Mechanisms and Therapeutic Approaches)

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Review

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17 pages, 1249 KiB

Open AccessFeature PaperReview

Pharmacological and Metabolic Significance of Bile Acids in Retinal Diseases

by Alice Win, Amanda Delgado, Ravirajsinh N. Jadeja, Pamela M. Martin, Manuela Bartoli and Menaka C. Thounaojam

Biomolecules 2021, 11(2), 292; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11020292 - 16 Feb 2021

Cited by 9 | Viewed by 3243

Abstract

Bile acids (BAs) are amphipathic sterols primarily synthesized from cholesterol in the liver and released in the intestinal lumen upon food intake. BAs play important roles in micellination of dietary lipids, stimulating bile flow, promoting biliary phospholipid secretion, and regulating cholesterol synthesis and elimination. Emerging evidence, however, suggests that, aside from their conventional biological function, BAs are also important signaling molecules and therapeutic tools. In the last decade, the therapeutic applications of BAs in the treatment of ocular diseases have gained great interest. Despite the identification of BA synthesis, metabolism, and recycling in ocular tissues, much remains unknown with regards to their biological significance in the eye. Additionally, as gut microbiota directly affects the quality of circulating BAs, their analysis could derive important information on changes occurring in this microenvironment. This review aims at providing an overview of BA metabolism and biological function with a focus on their potential therapeutic and diagnostic use for retinal diseases. Full article

(This article belongs to the Special Issue Ischemic Retinopathies: New Insights into Molecular Mechanisms and Therapeutic Approaches)

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