Prevention of Corneal Neovascularization by Adenovirus Encoding Human Vascular Endothelial Growth Factor Soluble Receptor (s-VEGFR1) in Lacrimal Gland

Abstract

The aims of this study were (1) to determine the efficacy of adenovirus vector serotype 5 (Ad) encoding human soluble VEGF receptor 1 (s-VEGFR1) gene transfer to the lacrimal gland (LG); (2) to investigate whether expression of s-VEGFR1 prevents corneal neovascularization (CNV) induced by alkali burns; and (3) to evaluate the safety of the procedure. METHODS. AdVEGFR1 vectors (25 lL, 1 3 10 10 pfu/mL) were injected in the right LGs of rats and were compared with AdNull vector (25 lL, 1 3 10 10 pfu/mL) or 25 lL of saline (Control) before cornea alkali burns with 1 M NaOH. After 7 days, CNV was documented at the slit lamp. Tear secretion was measured with phenol red threads. The animals were tested for s-VEGFR1 mRNA and protein in the LG by quantitative (q)PCR and immunohistochemistry staining, respectively. qPCR was used to compare the mRNA levels of IL-1b, IL-6, and TNF-a in the LG and ipsilateral trigeminal ganglion (TG). RESULTS. Ad-VEGFR1 transfected 83% (10/12) of the rats. VEGFR1 was present in LG acinar cells. CNV was prevented in 9 of 12 animals in the Ad-VEGFR1 group, compared with the Ad-Null (3:10) and Control groups (1:10) (P ¼ 0.0317). The tear secretion and cytokine mRNA levels in the LG and TG were similar in all three groups (P > 0.05). CONCLUSIONS. Adenoviral vector gene transfer was safe for LG structure and function. The LG as the target tissue showed local expression of human s-VEGFR1, and CNV was prevented in most of the eyes exposed to alkali burns.

Progress in Research on the Role of FGF in the Formation and Treatment of Corneal Neovascularization

“…We focused on alkali burns because of their severity. CNV can be caused by severe corneal alkali burn (Nominato et al, 2018), in which deep corneal stroma or full-thickness corneal injury is involved. In this situation, angiogenic factors play an important role in CNV.…”

Effect of ERK inhibitor on corneal neovascularization induced by alkali burn in mice and its mechanism

“…Thus, endothelial cells produce fibrinogen activators and stimulating blood vessels, which lead to the occurrence of angiogenesis. 6,7 In this research experiment, the model of CNV induced by alkali in mice was established. ERK inhibitors were used to interfere and investigate the effects and the mechanism of ERK inhibitors on neovascularization.…”

Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models

“…Therefore, the sVEGFR-1 exerts antiangiogenic, anti-edema, and anti-inflammatory activities, and its dysregulation has been associated with different pathological processes. For example, the expression of sVEGFR-1 by epithelial cells contributes to the corneal avascularity and its transfection in lacrimal glands has been shown to prevent the pathological corneal neovascularization [27,28]; the pathogenesis of pre-eclampsia, typically occurring in the last trimester of pregnancy, has been related to sVEGFR-1 production by placenta and subsequent neutralization of VEGF-A and PlGF signaling [29,30]; a low sVEGFR-1 to VEGF-A ratio has been correlated with higher tumor malignancy/invasiveness and poor patients' survival [31][32][33][34][35][36][37]. The sVEGFR-1 may also play a proangiogenic and protumoral action by activation of β1 integrin, which results in stimulation of endothelial cell adhesion and chemotaxis [38][39][40].…”