Corneal fibrosis: From in vitro models to current and upcoming drug and gene medicines

Trujillo Cubillo, Laura; Gurdal, Mehmet; Zeugolis, Dimitrios I.

doi:10.1016/j.addr.2024.115317

Cited by 1 publication

(2 citation statements)

References 261 publications

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“…There is "crosstalk" between the different TGF-β signaling pathways, such as between SMAD, MAPK (Mitogen-Activated Protein Kinase), Wnt, Notch, and JAK-STAT (Janus Kinase-Signal Transducer and Activator of Transcription), which is critical in orchestrating cellular responses during corneal wound healing [38]. Erk activity can regulate receptor-activated Smads, and the activation of JNK and p38 by TGF-β involves interactions with other signaling molecules such as TAK1 and TRAF6, demonstrating a complex network of interactions that modulate TGF-β mediated cellular responses to injury [39,40]. Studies have also highlighted the interaction between Substance P and TGF-β in human corneal fibroblasts, showing that Substance P promotes TGF-β-induced collagen synthesis, a necessary process in corneal fibrosis [22].…”

Section: Tgf-β Signaling Pathwaymentioning

confidence: 99%

“…Their results correlate the rich topological environment of the healthy cornea to myofibroblast transformation prevention. Understanding these mechanisms of regulation is paramount for developing therapeutic interventions to promote proper wound repair and prevent fibrosis [40] in the cornea. Disruptions in this crosstalk can lead to tissue remodeling abnormalities and scarring [41].…”

Section: Tgf-β Signaling Pathwaymentioning

confidence: 99%

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TGF-β-Based Therapies for Treating Ocular Surface Disorders

Ogata,

Verma,

Coulson-Thomas

et al. 2024

Cells

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The cornea is continuously exposed to injuries, ranging from minor scratches to deep traumas. An effective healing mechanism is crucial for the cornea to restore its structure and function following major and minor insults. Transforming Growth Factor-Beta (TGF-β), a versatile signaling molecule that coordinates various cell responses, has a central role in corneal wound healing. Upon corneal injury, TGF-β is rapidly released into the extracellular environment, triggering cell migration and proliferation, the differentiation of keratocytes into myofibroblasts, and the initiation of the repair process. TGF-β-mediated processes are essential for wound closure; however, excessive levels of TGF-β can lead to fibrosis and scarring, causing impaired vision. Three primary isoforms of TGF-β exist—TGF-β1, TGF-β2, and TGF-β3. Although TGF-β isoforms share many structural and functional similarities, they present distinct roles in corneal regeneration, which adds an additional layer of complexity to understand the role of TGF-β in corneal wound healing. Further, aberrant TGF-β activity has been linked to various corneal pathologies, such as scarring and Peter’s Anomaly. Thus, understanding the molecular and cellular mechanisms by which TGF-β1-3 regulate corneal wound healing will enable the development of potential therapeutic interventions targeting the key molecule in this process. Herein, we summarize the multifaceted roles of TGF-β in corneal wound healing, dissecting its mechanisms of action and interactions with other molecules, and outline its role in corneal pathogenesis.

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