Abstract
Purpose :
Currently, there is no approved drug therapy for corneal neovascularization (KNV). Anti-angiogenic drugs against vascular endothelial growth factor (VEGF) have been used off-label to treat KNV but with potential side effects on corneal epithelium and nerves. Secretogranin III (Scg3) was recently discovered as a disease-restricted angiogenic factor, and Scg3-neutralizing antibodies have been developed for disease-targeted therapy of other ocular angiogenic diseases with significant safety advantages. The purpose of this study is to determine and compare the efficacy of anti-Scg3 and anti-VEGF in mouse model of KNV.
Methods :
Alkali burn was performed on C57BL/6J mice to induced KNV. Mice were treated topically or subconjunctivally with anti-Scg3 humanized antibody (hAb), the anti-VEGF drug aflibercept, or phosphate buffered saline (PBS). To evaluate treatment efficacy, corneal images were taken on Day 5, 7, and 10 post alkali burn and analyzed for KNV score and total length of new vessels. Corneas were harvested on Day 10, immunostained for blood vessels using anti-CD31 mAb or for lymph vessels using anti-LYVE-1 mAb, imaged by confocal microscopy, and analyzed by ImageJ software.
Results :
Anti-Scg3 hAb significantly reduced total length of alkali burn-induced new corneal vessels by 78%. Aflibercept had similar efficacy to inhibit total length of new vessels by 60%. Immunostaining of corneas confirmed that anti-Scg3 hAb markedly reduced CD31 + corneal blood vessels and LYVE-1+ lymph vessels in alkali-burned corneas with similar efficacy to that of aflibercept treatment. In contrast, PBS control had no detectable therapeutic activity. No significant difference between limbal blood vessel number and density were observed between healthy mice and anti-Scg3-treated mice.
Conclusions :
These findings suggested that anti-Scg3 hAb and aflibercept significantly inhibit KNV with similar efficacy. In light of the disease-targeting property of anti-Scg3 hAb to selectively inhibit pathological angiogenesis with undetectable adverse effects on healthy vessels, neurons and epithelium, our findings warrant further investigation to compare the efficacy and safety of anti-Scg3 and aflibercept for anti-angiogenic therapy of KNV.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.