ArticleProceedings of the National Academy of Sciences of the United States of America2008
Role of TGF-beta in proliferative vitreoretinal diseases and ROCK as a therapeutic target.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 195 citations in OpenAlex.
- Article
- Pathogenic mechanisms and treatment advances in proliferative vitreoretinopathy: A review.Medicine · 2025Review
- Biogenesis, functional roles, and pathological implications of migrasomes.Cell death & disease · 2025Review
- Epigenetic Modifications in the Retinal Pigment Epithelium of the Eye During RPE-Related Regeneration or Retinal Diseases in Vertebrates.Biomedicines · 2025Review
- Liposome Encapsulation Enhances Ripasudil Therapeutic Efficacy Against Proliferative Vitreoretinal Diseases: Implications in Advanced Ocular Treatment.Investigative ophthalmology & visual science · 2025Article
- Fibrotic Changes in Rhegmatogenous Retinal Detachment.International journal of molecular sciences · 2025Review
- Knockdown of HSPA13 Inhibits TGFβ1-Induced Epithelial-Mesenchymal Transition of RPE by Suppressing the PI3K/Akt Signaling Pathway.Investigative ophthalmology & visual science · 2024Article
- An Association between HTRA1 and TGF-βJournal of clinical medicine · 2024Article
- Postoperative Proliferation Detection in Eyes Treated for Rhegmatogenous Retinal Detachment by WideField OCT Angiography.Translational vision science & technology · 2024Article
- The role of lipid peroxidation in epithelial-mesenchymal transition of retinal pigment epithelial cells.Scientific reports · 2024Article
- Redefining the ontogeny of hyalocytes as yolk sac-derived tissue-resident macrophages of the vitreous body.Journal of neuroinflammation · 2024Article
- Bone morphogenetic protein 6 (BMP6) antagonises experimental proliferative vitreoretinopathy established by TGF-β2 stimulation in retinal pigment epithelial cells through modulation of the p38 and JNK MAPK pathways.Cell and tissue research · 2024Article
- Short Term Effect of Pre-Operative Anti-VEGF on Angiogenic and Fibrotic Profile of Fibrovascular Membranes of Proliferative Diabetic Retinopathy.Investigative ophthalmology & visual science · 2024Article
- Integrative analysis of noncoding mutations identifies the druggable genome in preterm birth.Science advances · 2024Article
- Transition to Chronic Fibrosis in an Animal Model of Retinal Detachment With Features of Proliferative Vitreoretinopathy.Investigative ophthalmology & visual science · 2023Article
- The Effect of Anti-Autotaxin Aptamers on the Development of Proliferative Vitreoretinopathy.International journal of molecular sciences · 2023Article
- SIRT6 overexpression in the nucleus protects mouse retinal pigment epithelium from oxidative stress.Life science alliance · 2023Article
- A Useful Method for the Practice of Pneumatic Retinopexy: Slit-Lamp Laser Photocoagulation through the Gas Bubble.Journal of personalized medicine · 2023Article
- The essential role of N6-methyladenosine RNA methylation in complex eye diseases.Genes & diseases · 2023Review
- Applications of Human Amniotic Membrane Patching Assisted Vitrectomy in the Management of Postoperative PVR in Complex Retinal Detachments.Journal of clinical medicine · 2023Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Cicatricial contraction of preretinal fibrous membrane is a cause of severe vision loss in proliferative vitreoretinal diseases such as proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). TGF-beta is overexpressed in the vitreous of patients with proliferative vitreoretinal diseases and is also detectable in the contractile membranes. Therefore, TGF-beta is presumed to contribute to the cicatricial contraction of the membranes, however, the underlying mechanisms and TGF-beta's importance among various other factors remain to be elucidated. Vitreous samples from PDR or PVR patients caused significantly larger contraction of hyalocyte-containing collagen gels, compared with nonproliferative controls. The contractile effect was strongly correlated with the vitreal concentration of activated TGF-beta2 (r = 0.82, P < 0.0001). PDR or PVR vitreous promoted expression of alpha-smooth muscle actin (alpha-SMA) and phosphorylation of myosin light chain (MLC), a downstream mediator of Rho-kinase (ROCK), both of which were dramatically but incompletely suppressed by TGF-beta blockade. In contrast, fasudil, a potent and selective ROCK inhibitor, almost completely blocked the vitreous-induced MLC phosphorylation and collagen gel contraction. Fasudil disrupted alpha-SMA organization, but it did not affect its vitreal expression. In vivo, fasudil significantly inhibited the progression of experimental PVR in rabbit eyes without affecting the viability of retinal cells by electroretinographic and histological analyses. These results elucidate the critical role of TGF-beta in mediating cicatricial contraction in proliferative vitreoretinal diseases. ROCK, a key downstream mediator of TGF-beta and other factors might become a unique therapeutic target in the treatment of proliferative vitreoretinal diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.