{"doi":"10.3389/fopht.2024.1362601","title":"Editorial: Ocular fibrosis: molecular and cellular mechanisms and treatment modalities","abstract":"Tissue fibrosis occurs as an excessive repair response to mechanical damage, inflammation, ischemia, and degeneration leading to irreversible scar formation (1). The excessive proliferation and deposition of various extracellular matrix (ECM) proteins are mediated through transition of various cell types to myofibroblast-like cells. These cell types include epithelial cells, fibroblasts, vascular cells, glial cells, and inflammatory cells (4). The noted phenotypic and functional changes are considered major events during the fibrotic process with severe alterations in the tissue integrity and function (2,3). Fibrosis contributes to severity of pathologies in many chronic inflammatory diseases in the eye including retinopathy of prematurity, proliferative diabetic retinopathy (PDR), age-related macular degeneration (AMD), and glaucoma (1,5). Although the mechanisms of fibrogenesis have been extensively studied, the exact molecular and cellular events that drive this destructive tissue insult remain unresolved and may vary in a tissue, cell, and context dependent manner. Despite great advances in our knowledge regarding its etiology, effective treatment of fibrogenesis presents an unmet challenge.Numerous in vitro and in vivo models of fibrogenesis have helped gain insight into the role of various factors and their impact on intracellular mechanisms that drive the changes associated with fibrotic responses. Unfortunately, targeting of many of these cells and pathways has proven ineffective in prevention and reversal of fibrotic responses in various diseases.Numerous growth factors including TGF-β, PDGF, CTGF, VEGF-A, and TNF-α have profibrotic activity and contribute to ocular fibrosis through activation of their downstream signaling events (6). However, the unique contribution of these pathways and the target cells involved suggest a multi-step process whose involvement in different steps need further investigation. Although myofibroblasts are recognized as key cell types contributing to fibrosis, their sources remain unclear and may involve specific cell types in a uniquely tissue, cell, and organ specific manner. Thus, investigation of tissue and cell specific mechanisms are vital to identification of common and distinct contributors to fibrosis. This knowledge should aid in the development of more effective strategies to halt and/or reverse fibrotic responses associated with various chronic diseases.Recent studies in identifying the source of myofibroblasts, the key cell type driving fibrogenesis, have led to identification of perivascular supporting cells in many tissues in response to damage including diabetic retinopathy and age-related macular degeneration (7)(8)(9).However, the details of mechanisms for this selective transition of pericytes to myofibroblasts and the source of mediators involved in fibrogenesis need further investigation. One of the key pathways implicated in fibrogenesis involves increased production of TGF-β and its action through its canonical (Smad-dependent) and non-canonical (Smad-independent) pathways driving fibrosis. TGF-β is shown to impact the transition of various cell types including epithelial cells, vascular cells, and inflammatory cells to myofibroblast-like cells and enhance the production of various ECM proteins. These changes have a significant impact on the ECM milieu and the function and integrity of the tissue and cellular microenvironment. Retinal pigment epithelium (RPE) cell dysfunction contributes to many retinal diseases including PDR, vitreoretinopathy, macular damage, and retinal detachment (10). Higashijima et al Although these studies aid in our understanding of the cellular and molecular mechanisms that drive fibrogenesis, additional investigations are needed to further identify the target cells and pathways that drive their fibrogenic phenotype in a tissue and cell specific","journal":"Frontiers in Ophthalmology","year":2024,"id":493628,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1037744,"name":"Teri L. Belecky‐Adams","orcid":"0000-0003-1299-8448","position":1,"is_corresponding":false},{"id":382555,"name":"Nader Sheibani","orcid":"0000-0003-2723-9217","position":2,"is_corresponding":false},{"id":405229,"name":"Christine M. Sorenson","orcid":"0000-0001-8461-6619","position":0,"is_corresponding":true}],"reference_count":13,"raw_metadata":null,"created_at":"2026-07-19T02:09:03.883685Z","pmid":"38984111","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}