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Cells
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Angiogenesis and Inflammation in the Eye
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Angiogenesis and Inflammation in the Eye

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

Deadline for manuscript submissions: closed (20 January 2023) | Viewed by 18478

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; anti-angiogenic and anti-inflammatory compounds; dietary supplementation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Proper development of supply and metabolic demands of phototransduction, which are met by precisely localized and designed vascular networks, is critical to normal visual function. The endothelial cell number is normally stable, likely due to a balance between proangiogenic factors and antiangiogenic factors. When there is an imbalance between these two, pathology ensues.

In the eye, angiogenesis is a major cause of much ocular disease and blindness. It is a significant contributing factor in ocular diseases such as diabetic retinopathy, exudative AMD, corneal neovascularization, retinopathy of prematurity, just to mention a few. Angiogenesis goes hand in hand with inflammation. In fact, angiogenesis and inflammation are mutually dependent, and during inflammatory reactions, immune cells synthesize and secrete pro-angiogenic factors that promote neovascularization. Mechanisms underlying angiogenesis and inflammation, although extensively investigated in tumors, still remain a key issue in vascular diseases of the eye.

In the present issue, we focus on studies on ocular angiogenesis and inflammation and how their findings can be used to better maintain vascular networks in the eye and prevent retinal diseases by validating therapeutic approaches for neurovascular/inflammatory pathologies of the eye. In this Special Issue, different forms of angiogenesis/inflammatory diseases, their mediators, and implications for treatment will be considered by either experimental works or reviews in both animal models and human patients.

Prof. Paola Bagnoli
Guest Editor

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Keywords

  • ocular pathologies
  • retinal function
  • photoreceptor degeneration
  • animal models/human patients
  • neovessel formation
  • transcription factors/proangiogenic factors
  • inflammatory processes/pro-angiogenic cytokines
  • microglial activation/muller cell gliosis
  • anti-angiogenic/anti-inflammatory therapies
  • mechanism of action

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Published Papers (5 papers)

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Research

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15 pages, 2080 KiB  
Article
Protective Effect of NO2-OA on Oxidative Stress, Gliosis, and Pro-Angiogenic Response in Müller Glial Cells
by María V. Vaglienti, Paula V. Subirada, Mariana B. Joray, Gustavo Bonacci and María C. Sánchez
Cells 2023, 12(3), 494; https://doi.org/10.3390/cells12030494 - 2 Feb 2023
Cited by 6 | Viewed by 2050
Abstract
Inflammation and oxidative and nitrosative stress are involved in the pathogenesis of proliferative retinopathies (PR). In PR, a loss of balance between pro-angiogenic and anti-angiogenic factors favors the secretion of vascular endothelial growth factor (VEGF). This vascular change results in alterations in the [...] Read more.
Inflammation and oxidative and nitrosative stress are involved in the pathogenesis of proliferative retinopathies (PR). In PR, a loss of balance between pro-angiogenic and anti-angiogenic factors favors the secretion of vascular endothelial growth factor (VEGF). This vascular change results in alterations in the blood–retinal barrier, with extravasation of plasma proteins such as α2-macroglobulin (α2M) and gliosis in Müller glial cells (MGCs, such as MIO-M1). It is well known that MGCs play important roles in healthy and sick retinas, including in PR. Nitro-fatty acids are electrophilic lipid mediators with anti-inflammatory and cytoprotective properties. Our aim was to investigate whether nitro-oleic acid (NO2-OA) is beneficial against oxidative stress, gliosis, and the pro-angiogenic response in MGCs. Pure synthetic NO2-OA increased HO-1 expression in a time- and concentration-dependent manner, which was abrogated by the Nrf2 inhibitor trigonelline. In response to phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS), NO2-OA prevented the ROS increase and reduced the gliosis induced by α2M. Finally, when hypoxic MGCs were incubated with NO2-OA, the increase in VEGF mRNA expression was not affected, but under hypoxia and inflammation (IL-1β), NO2-OA significantly reduced VEGF mRNA levels. Furthermore, NO2-OA inhibited endothelial cell (BAEC) tubulogenesis. Our results highlight NO2-OA’s protective effect on oxidative damage, gliosis; and the exacerbated pro-angiogenic response in MGCs. Full article
(This article belongs to the Special Issue Angiogenesis and Inflammation in the Eye)
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18 pages, 2476 KiB  
Article
Etiological Roles of p75NTR in a Mouse Model of Wet Age-Related Macular Degeneration
by Paula Virginia Subirada, Albana Tovo, María Victoria Vaglienti, José Domingo Luna Pinto, Horacio Uri Saragovi, Maria Cecilia Sánchez, Agustín Anastasía and Pablo Federico Barcelona
Cells 2023, 12(2), 297; https://doi.org/10.3390/cells12020297 - 12 Jan 2023
Cited by 1 | Viewed by 2145
Abstract
Choroidal neovascularization (CNV) is a pathological angiogenesis of the choroidal plexus of the retina and is a key feature in the wet form of age-related macular degeneration. Mononuclear phagocytic cells (MPCs) are known to accumulate in the subretinal space, generating a chronic inflammatory [...] Read more.
Choroidal neovascularization (CNV) is a pathological angiogenesis of the choroidal plexus of the retina and is a key feature in the wet form of age-related macular degeneration. Mononuclear phagocytic cells (MPCs) are known to accumulate in the subretinal space, generating a chronic inflammatory state that promotes the growth of the choroidal neovasculature. However, how the MPCs are recruited and activated to promote CNV pathology is not fully understood. Using genetic and pharmacological tools in a mouse model of laser-induced CNV, we demonstrate a role for the p75 neurotrophin receptor (p75NTR) in the recruitment of MPCs, in glial activation, and in vascular alterations. After laser injury, expression of p75NTR is increased in activated Muller glial cells near the CNV area in the retina and the retinal pigmented epithelium (RPE)-choroid. In p75NTR knockout mice (p75NTR KO) with CNV, there is significantly reduced recruitment of MPCs, reduced glial activation, reduced CNV area, and the retinal function is preserved, as compared to wild type mice with CNV. Notably, a single intravitreal injection of a pharmacological p75NTR antagonist in wild type mice with CNV phenocopied the results of the p75NTR KO mice. Our results demonstrate that p75NTR is etiological in the development of CNV. Full article
(This article belongs to the Special Issue Angiogenesis and Inflammation in the Eye)
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Review

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21 pages, 2793 KiB  
Review
Cytochrome P450 1B1: A Key Regulator of Ocular Iron Homeostasis and Oxidative Stress
by Yong-Seok Song, Andrew J. Annalora, Craig B. Marcus, Colin R. Jefcoate, Christine M. Sorenson and Nader Sheibani
Cells 2022, 11(19), 2930; https://doi.org/10.3390/cells11192930 - 20 Sep 2022
Cited by 18 | Viewed by 4098
Abstract
Cytochrome P450 (CYP) 1B1 belongs to the superfamily of heme-containing monooxygenases. Unlike other CYP enzymes, which are highly expressed in the liver, CYP1B1 is predominantly found in extrahepatic tissues, such as the brain, and ocular tissues including retina and trabecular meshwork. CYP1B1 metabolizes [...] Read more.
Cytochrome P450 (CYP) 1B1 belongs to the superfamily of heme-containing monooxygenases. Unlike other CYP enzymes, which are highly expressed in the liver, CYP1B1 is predominantly found in extrahepatic tissues, such as the brain, and ocular tissues including retina and trabecular meshwork. CYP1B1 metabolizes exogenous chemicals such as polycyclic aromatic hydrocarbons. CYP1B1 also metabolizes endogenous bioactive compounds including estradiol and arachidonic acid. These metabolites impact various cellular and physiological processes during development and pathological processes. We previously showed that CYP1B1 deficiency mitigates ischemia-mediated retinal neovascularization and drives the trabecular meshwork dysgenesis through increased levels of oxidative stress. However, the underlying mechanisms responsible for CYP1B1-deficiency-mediated increased oxidative stress remain largely unresolved. Iron is an essential element and utilized as a cofactor in a variety of enzymes. However, excess iron promotes the production of hydroxyl radicals, lipid peroxidation, increased oxidative stress, and cell damage. The retinal endothelium is recognized as a major component of the blood–retinal barrier, which controls ocular iron levels through the modulation of proteins involved in iron regulation present in retinal endothelial cells, as well as other ocular cell types including trabecular meshwork cells. We previously showed increased levels of reactive oxygen species and lipid peroxidation in the absence of CYP1B1, and in the retinal vasculature and trabecular meshwork, which was reversed by administration of antioxidant N-acetylcysteine. Here, we review the important role CYP1B1 expression and activity play in maintaining retinal redox homeostasis through the modulation of iron levels by retinal endothelial cells. The relationship between CYP1B1 expression and activity and iron levels has not been previously delineated. We review the potential significance of CYP1B1 expression, estrogen metabolism, and hepcidin–ferroportin regulatory axis in the local regulation of ocular iron levels. Full article
(This article belongs to the Special Issue Angiogenesis and Inflammation in the Eye)
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13 pages, 302 KiB  
Review
Integrins: An Important Link between Angiogenesis, Inflammation and Eye Diseases
by Małgorzata Mrugacz, Anna Bryl, Mariusz Falkowski and Katarzyna Zorena
Cells 2021, 10(7), 1703; https://doi.org/10.3390/cells10071703 - 6 Jul 2021
Cited by 37 | Viewed by 4981
Abstract
Integrins belong to a group of cell adhesion molecules (CAMs) which is a large group of membrane-bound proteins. They are responsible for cell attachment to the extracellular matrix (ECM) and signal transduction from the ECM to the cells. Integrins take part in many [...] Read more.
Integrins belong to a group of cell adhesion molecules (CAMs) which is a large group of membrane-bound proteins. They are responsible for cell attachment to the extracellular matrix (ECM) and signal transduction from the ECM to the cells. Integrins take part in many other biological activities, such as extravasation, cell-to-cell adhesion, migration, cytokine activation and release, and act as receptors for some viruses, including severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). They play a pivotal role in cell proliferation, migration, apoptosis, tissue repair and are involved in the processes that are crucial to infection, inflammation and angiogenesis. Integrins have an important part in normal development and tissue homeostasis, and also in the development of pathological processes in the eye. This review presents the available evidence from human and animal research into integrin structure, classification, function and their role in inflammation, infection and angiogenesis in ocular diseases. Integrin receptors and ligands are clinically interesting and may be promising as new therapeutic targets in the treatment of some eye disorders. Full article
(This article belongs to the Special Issue Angiogenesis and Inflammation in the Eye)
21 pages, 1073 KiB  
Review
Future Perspectives of Therapeutic, Diagnostic and Prognostic Aptamers in Eye Pathological Angiogenesis
by Emilio Iturriaga-Goyon, Beatriz Buentello-Volante, Fátima Sofía Magaña-Guerrero and Yonathan Garfias
Cells 2021, 10(6), 1455; https://doi.org/10.3390/cells10061455 - 10 Jun 2021
Cited by 5 | Viewed by 4183
Abstract
Aptamers are single-stranded DNA or RNA oligonucleotides that are currently used in clinical trials due to their selectivity and specificity to bind small molecules such as proteins, peptides, viral particles, vitamins, metal ions and even whole cells. Aptamers are highly specific to their [...] Read more.
Aptamers are single-stranded DNA or RNA oligonucleotides that are currently used in clinical trials due to their selectivity and specificity to bind small molecules such as proteins, peptides, viral particles, vitamins, metal ions and even whole cells. Aptamers are highly specific to their targets, they are smaller than antibodies and fragment antibodies, they can be easily conjugated to multiple surfaces and ions and controllable post-production modifications can be performed. Aptamers have been therapeutically used for age-related macular degeneration, cancer, thrombosis and inflammatory diseases. The aim of this review is to highlight the therapeutic, diagnostic and prognostic possibilities associated with aptamers, focusing on eye pathological angiogenesis. Full article
(This article belongs to the Special Issue Angiogenesis and Inflammation in the Eye)
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