Prevention of corneal neovascularization by adenovirus encoding human vascular endothelial growth factor soluble receptor (s-VEGFR1) in lacrimal gland

Abstract

PURPOSE. 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 × 10 10 pfu/mL) were injected in the right LGs of rats and were compared with AdNull vector (25 lL, 1 × 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-1β, IL-6, and TNF-α 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 = 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.