Pigment Epithelium-Derived Factor-Loaded PEGylated Nanoparticles as a New Antiangiogenic Therapy for Neovascularization

Abstract

Background. Pathological neovascularization, which involves a disruption in the balance between angiogenic and antiangiogenic factors under pathological conditions, is the basis of many intraocular diseases. Pigment epithelium-derived factor (PEDF) is a potent natural, endogenous inhibitor of neovascularization because of its antiangiogenic and neuroprotective benefits. However, its application is restricted by its instability and short half-life. The present study is aimed at investigating the cytotoxicity and antiangiogenic effects of PEDF-loaded PEGylated nanoparticles (NP-PEG-PEDF) on high glucose-stimulated human umbilical vein endothelial cells (HUVECs). Methods. In this study, NP-PEG-PEDF were fabricated using the multiple emulsion method for the first time. HUVECs were cultured in a high concentration of glucose (30 mmol/L D-glucose), simulating diabetic conditions. The antiangiogenic effects of vascular endothelial growth factor (VEGF), pure PEDF, and NP-PEG-PEDF on proliferation, migration, and tube formation were evaluated. VEGF secretion in high glucose-stimulated HUVECs was further tested in vitro. Results. NP-PEG-PEDF exhibited low cytotoxicity in HUVECs. Our results indicated that in vitro, NP-PEG-PEDF attenuated diabetes-induced HUVEC proliferation, migration, and tube formation and suppressed VEGF secretion. The apoptosis of diabetes-induced HUVECs occurred in a dose-dependent manner, which showed a statistically significant difference compared with the PEDF treatment group. Conclusion. Our study is the first to demonstrate that NP-PEG-PEDF exert antiangiogenic effects on high glucose-stimulated HUVECs and have the potential to alleviate microvascular dysfunction. These data suggest that the NP-PEG-PEDF delivery system may offer an innovative therapeutic strategy for preventing neovascularization of the fundus.

Prolactin Expression in the Baboon (Papio hamadryas) Eye

“…Although, there are no studies showing if the retinal cell lines that express PRL also express vasoinhibins, the presence of the hormone can be interpreted as evidence that these peptides could be generated by proteolysis of PRL [ 18 , 28 ]. This theory is supported by reports demonstrating that the retinal expression of PEDF (pigmented epithelium-derived factor) in RPE and GCL acts as an antiangiogenic factor [ 30 , 31 , 34 , 43 , 44 ]. A novel function of vasoinhibins as inhibitors of the increased retinal VEGF-induced vasopermeability associated with diabetic retinopathy suggests that vasoinhibins can be developed as new therapeutic agents to control the excessive retinal vasopermeability observed in diabetic retinopathy and other vasoproliferative retinopathies [ 23 , 25 , 26 , 31 ].…”

m6A reader IGF2BP1 accelerates apoptosis of high glucose-induced vascular endothelial cells in a m6A-HMGB1 dependent manner

“…Human umbilical vascular endothelium cells (HUVEC) were purchased from ScienCell Research Laboratories (Carlsbad, CA, USA) and maintained in Endothelial Cell Medium (ECM, Carlsbad, CA, USA) added with 10% fetal bovine serum (FBS; Gibco, Billings, MT, USA) and 5.6 mmol/L glucose. The diabetes model treatment was performed as previously described ( Li et al, 2015 ; Zhao et al, 2022 ). For diabetes group (high glucose, HG), HUVECs were exposed to 30 mmol/L d-glucose.…”

Advancements in Neovascular Ophthalmopathy: Therapeutic Strategies and Future Prospects

“…In recent years, Zhao Feng et al have constructed PEDF-loaded polyethylene glycol nanoparticles that effectively inhibit the migration, proliferation, and tube formation of human umbilical vein endothelial cells (HUVECs) stimulated by high glucose. This opens up innovative therapeutic approaches for future neovascular eye diseases [172] . Additionally, PEDF-derived short synthetic peptides retain anti-angiogenic activity and may be more suitable as anti-angiogenic drugs than the full PEDF protein [173] .…”