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Understanding the role of transcription factors in PVDs is essential for managing severe vision-threatening conditions like proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). These disorders involve the formation of fibrovascular membranes that often cause tractional retinal detachment. Consequently, researchers focus on the epithelial-to-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells as a primary driver. A complex network of transcription factors (TFs) orchestrates this transition, leading to significant structural changes in the eye.
The transcription factor ZEB1 acts as a pivotal regulator in this pathological process. Specifically, it represses epithelial markers such as E-cadherin while inducing mesenchymal markers like N-cadherin and vimentin. This shift promotes cell migration and fibrotic membrane formation. Furthermore, NFAT5 contributes by mediating osmotic stress responses and upregulating inflammatory cytokines. These cytokines then accelerate the EMT and fibrotic pathways. Additionally, factors like HIF-1α and AP-1 drive inflammation and extracellular matrix (ECM) remodeling.
Maintaining RPE cell identity is equally important for ocular health. Transcription factors such as KLF4 and MITF are vital for this stability. However, pathological conditions often lead to their downregulation. This disruption breaks down epithelial integrity and predisposes cells to undergo EMT. Moreover, β-catenin reinforces this progression through the Wnt signaling pathway. Finally, proteins like AEBP1 and ZFP36L1 offer novel post-transcriptional targets. Targeting these synergistic interactions provides a promising avenue for multi-targeted therapies.
Transcription factors drive the transformation of RPE cells into migratory mesenchymal cells. This process forms fibrotic membranes that exert traction on the retina, eventually leading to detachment.
Yes. Inhibiting specific factors like ZEB1 or NFAT5 may prevent the fibrotic changes seen in PVDs. Researchers are currently exploring these pathways to develop non-invasive, multi-targeted treatments.
Disclaimer: This content is for informational and educational purposes only. It is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.
References
Duveau C et al. Key role of transcription factors network in proliferative vitreoretinal diseases development. Cell Biosci. 2026 May 08. doi: 10.1186/s13578-026-01581-4. PMID: 42104523.
Kobayashi M et al. Suppression of Epithelial-Mesenchymal Transition in Retinal Pigment Epithelial Cells by an MRTF-A Inhibitor. Invest Ophthalmol Vis Sci. 2019;60(2):528-537. doi: 10.1167/iovs.18-25678.
Temple S et al. Epigenomic and Transcriptomic Changes During Human RPE EMT in a Stem Cell Model of Epiretinal Membrane Pathogenesis and Prevention by Nicotinamide. Commun Biol. 2020 Apr 02. doi: 10.1038/s42003-020-0857-4.
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