Cargando…

Understanding Drivers of Ocular Fibrosis: Current and Future Therapeutic Perspectives

Ocular fibrosis leads to severe visual impairment and blindness worldwide, being a major area of unmet need in ophthalmology and medicine. To date, the only available treatments are antimetabolite drugs that have significant potentially blinding side effects, such as tissue damage and infection. The...

Descripción completa

Detalles Bibliográficos
Autores principales: Mallone, Fabiana, Costi, Roberta, Marenco, Marco, Plateroti, Rocco, Minni, Antonio, Attanasio, Giuseppe, Artico, Marco, Lambiase, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584003/
https://www.ncbi.nlm.nih.gov/pubmed/34769176
http://dx.doi.org/10.3390/ijms222111748
_version_ 1784597340869361664
author Mallone, Fabiana
Costi, Roberta
Marenco, Marco
Plateroti, Rocco
Minni, Antonio
Attanasio, Giuseppe
Artico, Marco
Lambiase, Alessandro
author_facet Mallone, Fabiana
Costi, Roberta
Marenco, Marco
Plateroti, Rocco
Minni, Antonio
Attanasio, Giuseppe
Artico, Marco
Lambiase, Alessandro
author_sort Mallone, Fabiana
collection PubMed
description Ocular fibrosis leads to severe visual impairment and blindness worldwide, being a major area of unmet need in ophthalmology and medicine. To date, the only available treatments are antimetabolite drugs that have significant potentially blinding side effects, such as tissue damage and infection. There is thus an urgent need to identify novel targets to prevent/treat scarring and postsurgical fibrosis in the eye. In this review, the latest progress in biological mechanisms underlying ocular fibrosis are discussed. We also summarize the current knowledge on preclinical studies based on viral and non-viral gene therapy, as well as chemical inhibitors, for targeting TGFβ or downstream effectors in fibrotic disorders of the eye. Moreover, the role of angiogenetic and biomechanical factors in ocular fibrosis is discussed, focusing on related preclinical treatment approaches. Moreover, we describe available evidence on clinical studies investigating the use of therapies targeting TGFβ-dependent pathways, angiogenetic factors, and biomechanical factors, alone or in combination with other strategies, in ocular tissue fibrosis. Finally, the recent progress in cell-based therapies for treating fibrotic eye disorders is discussed. The increasing knowledge of these disorders in the eye and the promising results from testing of novel targeted therapies could offer viable perspectives for translation into clinical use.
format Online
Article
Text
id pubmed-8584003
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-85840032021-11-12 Understanding Drivers of Ocular Fibrosis: Current and Future Therapeutic Perspectives Mallone, Fabiana Costi, Roberta Marenco, Marco Plateroti, Rocco Minni, Antonio Attanasio, Giuseppe Artico, Marco Lambiase, Alessandro Int J Mol Sci Review Ocular fibrosis leads to severe visual impairment and blindness worldwide, being a major area of unmet need in ophthalmology and medicine. To date, the only available treatments are antimetabolite drugs that have significant potentially blinding side effects, such as tissue damage and infection. There is thus an urgent need to identify novel targets to prevent/treat scarring and postsurgical fibrosis in the eye. In this review, the latest progress in biological mechanisms underlying ocular fibrosis are discussed. We also summarize the current knowledge on preclinical studies based on viral and non-viral gene therapy, as well as chemical inhibitors, for targeting TGFβ or downstream effectors in fibrotic disorders of the eye. Moreover, the role of angiogenetic and biomechanical factors in ocular fibrosis is discussed, focusing on related preclinical treatment approaches. Moreover, we describe available evidence on clinical studies investigating the use of therapies targeting TGFβ-dependent pathways, angiogenetic factors, and biomechanical factors, alone or in combination with other strategies, in ocular tissue fibrosis. Finally, the recent progress in cell-based therapies for treating fibrotic eye disorders is discussed. The increasing knowledge of these disorders in the eye and the promising results from testing of novel targeted therapies could offer viable perspectives for translation into clinical use. MDPI 2021-10-29 /pmc/articles/PMC8584003/ /pubmed/34769176 http://dx.doi.org/10.3390/ijms222111748 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mallone, Fabiana
Costi, Roberta
Marenco, Marco
Plateroti, Rocco
Minni, Antonio
Attanasio, Giuseppe
Artico, Marco
Lambiase, Alessandro
Understanding Drivers of Ocular Fibrosis: Current and Future Therapeutic Perspectives
title Understanding Drivers of Ocular Fibrosis: Current and Future Therapeutic Perspectives
title_full Understanding Drivers of Ocular Fibrosis: Current and Future Therapeutic Perspectives
title_fullStr Understanding Drivers of Ocular Fibrosis: Current and Future Therapeutic Perspectives
title_full_unstemmed Understanding Drivers of Ocular Fibrosis: Current and Future Therapeutic Perspectives
title_short Understanding Drivers of Ocular Fibrosis: Current and Future Therapeutic Perspectives
title_sort understanding drivers of ocular fibrosis: current and future therapeutic perspectives
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584003/
https://www.ncbi.nlm.nih.gov/pubmed/34769176
http://dx.doi.org/10.3390/ijms222111748
work_keys_str_mv AT mallonefabiana understandingdriversofocularfibrosiscurrentandfuturetherapeuticperspectives
AT costiroberta understandingdriversofocularfibrosiscurrentandfuturetherapeuticperspectives
AT marencomarco understandingdriversofocularfibrosiscurrentandfuturetherapeuticperspectives
AT platerotirocco understandingdriversofocularfibrosiscurrentandfuturetherapeuticperspectives
AT minniantonio understandingdriversofocularfibrosiscurrentandfuturetherapeuticperspectives
AT attanasiogiuseppe understandingdriversofocularfibrosiscurrentandfuturetherapeuticperspectives
AT articomarco understandingdriversofocularfibrosiscurrentandfuturetherapeuticperspectives
AT lambiasealessandro understandingdriversofocularfibrosiscurrentandfuturetherapeuticperspectives