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      Wound Healing Response After Bleb-Forming Glaucoma Surgery With a SIBS Microshunt in Rabbits

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          Abstract

          Purpose

          The PreserFlo MicroShunt is an innovative implant for the surgical treatment of glaucoma. Although usually effective, surgeries can still fail due to fibrosis. This study was conducted to gain insight into the histological aspects of the fibrotic response and find potential targets to reduce postoperative fibrosis.

          Methods

          Fifteen New Zealand White rabbits were implanted with a microshunt and followed up for 40 days. Animals were euthanized at postoperative days (PODs) 1, 5, and 40 to collect eyes for histological evaluation. Bleb formation and ocular health were assessed by slit-lamp (SL) biomicroscopy and optical coherence tomography (OCT). Intraocular pressure (IOP) was measured using rebound tonometry.

          Results

          Blebs failed after approximately 2 weeks based on bleb survival and IOP measurements. No severe complications were observed with OCT and SL. Histology revealed a wide variety of cells, in the bleb and around the microshunt, including polymorphonuclear leucocytes (PMNs), myofibroblasts, and foreign body giant cells, at different PODs.

          Conclusions

          Implantation of a poly(styrene- b-isobutylene- b-styrene) microshunt in rabbits resulted in the occurrence of a wide variety of cells during the wound-healing response. Future research should further elucidate the potential of these (earlier often overlooked) cells to target the fibrotic response in vivo—for example, by developing novel antifibrotic drugs, methods for sustained delivery of medications, or augmenting material properties.

          Translational Relevance

          Current antifibrotic therapies aim to inhibit myofibroblasts; however, a wide variety of cells are involved in the fibrotic response. Future research focusing on these cells could offer novel methods for reducing the fibrotic response after glaucoma surgery.

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          Most cited references49

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          Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis.

          Glaucoma is the leading cause of global irreversible blindness. Present estimates of global glaucoma prevalence are not up-to-date and focused mainly on European ancestry populations. We systematically examined the global prevalence of primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), and projected the number of affected people in 2020 and 2040. Systematic review and meta-analysis. Data from 50 population-based studies (3770 POAG cases among 140,496 examined individuals and 786 PACG cases among 112 398 examined individuals). We searched PubMed, Medline, and Web of Science for population-based studies of glaucoma prevalence published up to March 25, 2013. Hierarchical Bayesian approach was used to estimate the pooled glaucoma prevalence of the population aged 40-80 years along with 95% credible intervals (CrIs). Projections of glaucoma were estimated based on the United Nations World Population Prospects. Bayesian meta-regression models were performed to assess the association between the prevalence of POAG and the relevant factors. Prevalence and projection numbers of glaucoma cases. The global prevalence of glaucoma for population aged 40-80 years is 3.54% (95% CrI, 2.09-5.82). The prevalence of POAG is highest in Africa (4.20%; 95% CrI, 2.08-7.35), and the prevalence of PACG is highest in Asia (1.09%; 95% CrI, 0.43-2.32). In 2013, the number of people (aged 40-80 years) with glaucoma worldwide was estimated to be 64.3 million, increasing to 76.0 million in 2020 and 111.8 million in 2040. In the Bayesian meta-regression model, men were more likely to have POAG than women (odds ratio [OR], 1.36; 95% CrI, 1.23-1.52), and after adjusting for age, gender, habitation type, response rate, and year of study, people of African ancestry were more likely to have POAG than people of European ancestry (OR, 2.80; 95% CrI, 1.83-4.06), and people living in urban areas were more likely to have POAG than those in rural areas (OR, 1.58; 95% CrI, 1.19-2.04). The number of people with glaucoma worldwide will increase to 111.8 million in 2040, disproportionally affecting people residing in Asia and Africa. These estimates are important in guiding the designs of glaucoma screening, treatment, and related public health strategies. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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            The basics of epithelial-mesenchymal transition.

            The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.
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              The role of endothelial-to-mesenchymal transition in cancer progression

              Recent evidence has demonstrated that endothelial-to-mesenchymal transition (EndMT) may have a significant role in a number of diseases. Although EndMT has been previously studied as a critical process in heart development, it is now clear that EndMT can also occur postnatally in various pathologic settings, including cancer and cardiac fibrosis. During EndMT, resident endothelial cells delaminate from an organised cell layer and acquire a mesenchymal phenotype characterised by loss of cell–cell junctions, loss of endothelial markers, gain of mesenchymal markers, and acquisition of invasive and migratory properties. Endothelial-to-mesenchymal transition -derived cells are believed to function as fibroblasts in damaged tissue, and may therefore have an important role in tissue remodelling and fibrosis. In tumours, EndMT is an important source of cancer-associated fibroblasts (CAFs), which are known to facilitate tumour progression in several ways. These new findings suggest that targeting EndMT may be a novel therapeutic strategy, which is broadly applicable not only to cancer but also to various other disease states.
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                Author and article information

                Journal
                Transl Vis Sci Technol
                Transl Vis Sci Technol
                TVST
                Translational Vision Science & Technology
                The Association for Research in Vision and Ophthalmology
                2164-2591
                26 August 2022
                August 2022
                : 11
                : 8
                : 29
                Affiliations
                [1 ]University Eye Clinic Maastricht, Maastricht University Medical Center+, Maastricht, the Netherlands
                [2 ]Department of Ophthalmology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands
                [3 ]Chemelot Institute for Science and Technology, Maastricht, the Netherlands
                [4 ]Department of Pathology, Cardiovascular Research Institute Maastricht, School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands
                [5 ]Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
                [6 ]InnFocus, Inc., Miami, FL, USA
                Author notes
                [* ] Correspondence: Ralph J. S. van Mechelen, University Eye Clinic Maastricht, Maastricht University Medical Center+, P. Debyelaan 25, 6202 AZ Maastricht, the Netherlands. e-mail: r.vanmechelen@ 123456maastrichtuniversity.nl
                Article
                TVST-22-4497
                10.1167/tvst.11.8.29
                9428362
                36018582
                6511ae29-529c-468a-94e8-b2314495f3a1
                Copyright 2022 The Authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 15 July 2022
                : 11 February 2022
                Page count
                Pages: 11
                Categories
                Glaucoma
                Glaucoma

                glaucoma surgery,wound-healing response,animal model,microshunt,fibrosis

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