Anti-scarring effects of conbercept on human Tenon's fibroblasts: comparisons with bevacizumab
Lei Zuo1, Shaopin Zhu2, Shengjie Gu1
1Department of Ophthalmology, Shanghai Fourth People's Hospital, Tongji University School of Medicine, No. 1279, Sanmen road, Shanghai, 200434, China.
Background:
Safely inhibiting the formation of scar in the glaucoma filtration surgery (GFS) has always been an issue for clinical glaucoma doctors. Anti-vascular endothelial growth factor (VEGF) agents can reduce angiogenesis, and anti-placental growth factor (PIGF) agents can affect reactive gliosis. However, the effect of conbercept, which can bind to both VEGF and PIGF, on human Tenon's fibroblasts (HTFs) is unknown.
Methods:
HTFs were cultured in vitro and treated with conbercept or bevacizumab (BVZ). No drug was added to the control group. The effects of drugs on cell proliferation were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the collagen type I alpha1(Col1A1) mRNA expression level was measured using quantitative polymerase chain reaction (qPCR). HTF cell migration after drug interventions was evaluated using the scratch wound assay along with the measurement of the expression levels of VEGF and PIGF in human umbilical vein endothelial cells (HUVECs) using enzyme-linked immunosorbent assay, as well as the detection of the VEGF(R) mRNA expression level in HTFs using qPCR.
Results:
After the addition of conbercept (0.01, 0.1, and 1 mg/mL) to the cultured HTFs or HUVECs, no significant cytotoxicity was observed compared with the control group, while the cytotoxicity of 2.5 mg/mL BVZ on HTFs was obvious. Conbercept significantly inhibited HTF cell migration and Col1A1 mRNA expression level in HTFs. It was superior to BVZ in inhibiting HTF migration. After the intervention with conbercept, the expression level of PIGF and VEGF in HUVECs significantly decreased; and the inhibitory effect of conbercept on the expression level of VEGF in HUVECs was weaker than that of BVZ. Conbercept was more advantageous than BVZ in inhibiting the expression level of VEGFR-1 mRNA in HTFs. However, its effect in terms of inhibiting the expression level of VEGFR-2 mRNA in HTFs was weaker than that of BVZ.
Conclusion:
The results suggested the low cytotoxicity and significant anti-scarring effect of conbercept in HTF with significant anti-PIGF and inferior anti-VEGF effects compared with BVZ, thus providing a better understanding of the role of conbercept in the GFS wound healing process.
Insights
Conbercept shows low cytotoxicity and effectively inhibits scar formation in glaucoma surgery by reducing fibroblast migration and collagen production. It targets both placental growth factor (PIGF) and vascular endothelial growth factor (VEGF), offering a promising anti-scarring effect.
Area of Science:
- Ophthalmology
- Cell Biology
- Regenerative Medicine
Background:
- Glaucoma filtration surgery (GFS) scar formation presents a clinical challenge.
- Anti-VEGF and anti-PIGF agents are used, but conbercept's effect on human Tenon's fibroblasts (HTFs) is unstudied.
Purpose of the Study:
- To investigate the effects of conbercept on HTFs, focusing on its anti-scarring potential.
- To compare conbercept's efficacy with bevacizumab (BVZ) in inhibiting fibroblast activity.
Main Methods:
- HTFs were treated with conbercept or BVZ.
- Cell proliferation (MTT assay), collagen mRNA expression (qPCR), and cell migration (scratch assay) were assessed.
- VEGF/PIGF levels in HUVECs and VEGFR mRNA in HTFs were measured.
Main Results:
- Conbercept exhibited low cytotoxicity, unlike BVZ.
- Conbercept significantly inhibited HTF migration and collagen production, outperforming BVZ in migration inhibition.
- Conbercept reduced VEGF and PIGF levels in HUVECs but was less effective than BVZ for VEGF. It inhibited VEGFR-1 mRNA more effectively than BVZ but VEGFR-2 less effectively.
Conclusions:
- Conbercept demonstrates low cytotoxicity and significant anti-scarring properties in HTFs.
- It offers a dual effect on PIGF and VEGF pathways, with distinct advantages over BVZ in specific mechanisms relevant to GFS wound healing.
