Aim: To investigate whether anti-placental growth factor (PGF) can inhibit subretinal fibrosis and whether this effect is mediated by the inhibitory effect of PGF on epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells.
Methods: Subretinal fibrosis model was established in laser induced choroidal neovascularization (CNV) mice on day 21 after laser photocoagulation. Immunofluorescence staining (IFS) of cryosections and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of PGF. IFS of whole choroidal flat-mounts was used to detect the degree of subretinal fibrosis. IFS of cryosections and ELISA were used to detect the expression of EMT related indicators in subretinal fibrosis lesions.
Results: The expression of PGF protein in subretinal fibrosis lesions was significantly up-regulated (<0.05), and mainly co-stained with pan-cytokeratin labeled RPE cells. Intravitreal injection of anti-PGF neutralizing antibody reduced the area of subretinal fibrosis and the ratio of fibrotic/angiogenic area significantly at the concentrations of 0.25, 0.5, 1.0, and 2.0 µg/µL (all <0.05). The expression of E-cadherin in the local RPE cells decreased, while α-SMA increased significantly in subretinal fibrosis lesions, and the application of anti-PGF neutralizing antibody could reverse these changes (<0.05).
Conclusion: The expression of PGF is up-regulated in the lesion site of subretinal fibrosis and mainly expressed in RPE cells. Intravitreal injection of anti-PGF neutralizing antibody can significantly inhibit the degree of subretinal fibrosis in CNV mice, and this effect may be mediated by the inhibition of PGF on EMT of RPE cells.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818457 | PMC |
| http://dx.doi.org/10.18240/ijo.2022.02.01 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
circSIRT2/miR-542-3p/VASH1 axis regulates endothelial-to-mesenchymal transition (EndMT) in subretinal fibrosis in age-related macular degeneration models.
Aging Cell
January 2025
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Neovascular age-related macular degeneration (nAMD), characterized by choroidal neovascularization (CNV), is one of the leading causes of severe visual impairment and irreversible vision loss around the world. Subretinal fibrosis (SRF) contributes to the incomplete response to anti-vascular endothelial growth factor (VEGF) treatment and is one of the main reasons for long-term poor visual outcomes in nAMD. Reducing SRF is urgently needed in the anti-VEGF era.
View Article and Find Full Text PDFRationally Engineering Pro-Proteins and Membrane-Penetrating α‑Helical Polypeptides for Genome Editing Toward Choroidal Neovascularization Treatment.
Adv Mater
December 2024
Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Ribonucleoprotein (RNP)-based CRISPR/Cas9 genome editing holds great potential for the treatment of choroidal neovascularization (CNV), which however, is challenged by the lack of efficient cytosolic protein delivery tools. Herein, reversibly-phosphorylated pro-proteins (P-proteins) with conjugated adenosine triphosphate (ATP) tags are engineered and coupled with a membrane-penetrating, guanidine-enriched, α-helical polypeptide (GP) to mediate robust and universal cytosolic delivery. GP forms salt-stable nanocomplexes (NCs) with P-proteins via electrostatic interaction and salt bridging, and the helix-assisted, strong membrane activities of GP enabled efficient cellular internalization and endolysosomal escape of NCs.
View Article and Find Full Text PDFEmerging clinical evidence of a dual role for Ang-2 and VEGF-A blockade with faricimab in retinal diseases.
Graefes Arch Clin Exp Ophthalmol
December 2024
Doheny Eye Institute, University of California, Los Angeles, 150 N. Orange Grove Blvd, Suite 232, Pasadena, CA, USA.
Anti-vascular endothelial growth factor (VEGF) therapies have transformed the treatment of retinal diseases. However, VEGF signaling is only one component of the complex, multifactorial pathophysiology of retinal diseases, and many patients have residual disease activity despite ongoing anti-VEGF treatment. The angiopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor receptor-2 (Ang/Tie2) signaling pathway is critical to endothelial cell homeostasis, survival, integrity, and vascular stability.
View Article and Find Full Text PDFAssessment of distributions and gender difference in adverse events related to faricimab: a real-world study based on FDA adverse event reporting system.
Expert Opin Drug Saf
December 2024
Geriatric Diseases Institute of Chengdu/Cancer Prevention and Treatment Institute of Chengdu, Department of Ophthalmology, Chengdu Fifth People's Hospital (The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China.
Background: Faricimab is a novel bispecific antibody drug for treating retinal disease. We aim to study the adverse events of faricimab based on the FDA Adverse Event Reporting System (FAERS) database.
Research Design And Methods: The FAERS data from 2020 to 2024 was extracted to conduct disproportionality analysis.
Analysis of factors affecting prognosis of the visual acuity and baseline risk factors for subretinal fibrosis in neovascular age-related macular degeneration patients.
Front Med (Lausanne)
November 2024
Department of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Background: To evaluate factors affecting visual acuity prognosis in patients with neovascular age-related macular degeneration (nAMD) following anti-vascular endothelial growth factor (anti-VEGF) therapy via intravitreal injection and to identify baseline risk factors for subretinal fibrosis (SF).
Methods: A retrospective study of 64 nAMD eyes treated with intravitreal anti-VEGF treatment over 12 months of follow-up was conducted. Demographic and optical coherence tomography characteristics at baseline were recorded to explore the relevant factors affecting visual acuity outcome.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!