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      Progress in Research on the Role of FGF in the Formation and Treatment of Corneal Neovascularization

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          Abstract

          Corneal neovascularization (CNV) is a sight-threatening disease usually associated with inflammatory, infectious, degenerative, and traumatic disorders of the ocular surface. Fibroblast growth factor (FGF) family members play an important role in angiogenesis to induce corneal neovascularization, which significantly affects the differentiation, proliferation, metastasis, and chemotaxis of vascular endothelial cells. Both acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) demonstrate positive staining in capillaries and induce corneal stromal cells. The anabolism of endothelial cells is induced by bFGF in corneal neovascularization. FGFs exert their effects via specific binding to cell surface-expressed specific receptors. We believe that both anti-FGF antibodies and anti-FGF receptor antibodies represent new directions for the treatment of CNV. Similar to anti-vascular endothelial growth factor antibodies, subconjunctival injection and eye drops can be considered effective forms of drug delivery.

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          Evolution of the Fgf and Fgfr gene families.

          Nobuyuki Itoh, David M. Ornitz (2004)
          Fibroblast growth factors (Fgfs) and Fgf receptors (Fgfrs) comprise a signaling system that is conserved throughout metazoan evolution. Twenty-two Fgfs and four Fgfrs have been identified in humans and mice. During evolution, the Fgf family appears to have expanded in two phases. In the first phase, during early metazoan evolution, Fgfs expanded from two or three to six genes by gene duplication. In the second phase, during the evolution of early vertebrates, the Fgf family expanded by two large-scale gen(om)e duplications. By contrast, the Fgfr family has expanded only in the second phase. However, the acquisition of alternative splicing by Fgfrs has increased their functional diversity. The mechanisms that regulate alternative splicing have been conserved since the divergences of echinoderms and vertebrates. The expansion of the Fgf and Fgfr gene families has enabled this signaling system to acquire functional diversity and, therefore, an almost ubiquitous involvement in developmental and physiological processes.
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            Corneal neovascularization.

            Jin-Hong Chang, Eric Gabison, Takuji Kato … (2001)
            Corneal neovascularization (NV) is a sight-threatening condition usually associated with inflammatory or infectious disorders of the ocular surface. It has been shown in the field of cancer angiogenesis research that a balance exists between angiogenic factors (such as fibroblast growth factor and vascular endothelial growth factor) and anti-angiogenic molecules (such as angiostatin, endostatin, or pigment epithelium derived factor) in the cornea. Several inflammatory, infectious, degenerative, and traumatic disorders are associated with corneal NV, in which the balance is tilted towards angiogenesis. The pathogenesis of corneal NV may be influenced by matrix metalloproteinases and other proteolytic enzymes. New medical and surgical treatments, including angiostatic steroids, nonsteroidal inflammatory agents, argon laser photocoagulation, and photodynamic therapy have been effective in animal models to inhibit corneal NV and transiently restore corneal "angiogenic privilege."
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              Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I.

              Z. Zhou, S S Apte, R Soininen … (2000)
              Membrane-type matrix metalloproteinase I (MT1-MMP)-deficient mice were found to have severe defects in skeletal development and angiogenesis. The craniofacial, axial, and appendicular skeletons were severely affected, leading to a short and domed skull, marked deceleration of postnatal growth, and death by 3 wk of age. Shortening of bones is a consequence of decreased chondrocyte proliferation in the proliferative zone of the growth plates. Defective vascular invasion of cartilage leads to enlargement of hypertrophic zones of growth plates and delayed formation of secondary ossification centers in long bones. In an in vivo corneal angiogenesis assay, null mice did not have angiogenic response to implanted FGF-2, suggesting that the defect in angiogenesis is not restricted to cartilage alone. In tissues from null mice, activation of latent matrix metalloproteinase 2 was deficient, suggesting that MT1-MMP is essential for its activation in vivo.
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Pharmacol
                Journal ID (iso-abbrev): Front Pharmacol
                Journal ID (publisher-id): Front. Pharmacol.
                Title: Frontiers in Pharmacology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1663-9812
                Publication date (Electronic): 25 February 2020
                Publication date Collection: 2020
                Volume: 11
                Electronic Location Identifier: 111
                Affiliations
                [1] Department of Ophthalmology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University , Wenzhou, China
                Author notes

                Edited by: Saverio Bellusci, University of Giessen, Germany

                Reviewed by: Elie El Agha, University of Giessen, Germany; Tingting Yuan, University of Alabama at Birmingham, United States

                *Correspondence: Haihua Zheng, eyezhh@ 123456126.com

                This article was submitted to Translational Pharmacology, a section of the journal Frontiers in Pharmacology

                Article
                DOI: 10.3389/fphar.2020.00111
                PMC ID: 7052042
                PubMed ID: 32158390
                SO-VID: 7b9a4133-2896-4205-98c5-a2a68b2969e1
                Copyright © Copyright © 2020 Chen, Bao, Zhao, Cao and Zheng
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 23 October 2019
                Date accepted : 28 January 2020
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 49, Pages: 6, Words: 3017
                Categories
                Subject: Pharmacology
                Subject: Review

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: corneal neovascularization,fibroblast growth factor,development,treatment,drug delivery
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: corneal neovascularization, fibroblast growth factor, development, treatment, drug delivery

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