Abstract
Purpose :
Currently, there is no approved drug for corneal neovascularization (CoNV), and existing drugs are ineffective in treating corneal opacity. Anti-VEGF drugs treat CoNV but with potential side effects on corneal epithelium and nerves. In contrast, anti-Scg3-neutralizing antibodies, developed for disease-targeted therapy of ocular angiogenic diseases, offer significant safety advantages. This study aims to characterize the efficacy of secretogranin III (Scg3)-neutralizing antibodies in inhibiting CoNV and opacity in a mouse alkali burn model and to compare the efficacy to that of the anti-VEGF drug aflibercept.
Methods :
Male C57BL/6J mice were divided randomly into 3 groups (N=10) after an alkali burn on the right eye. The mice were treated subconjunctivally with anti-Scg3 humanized antibody (hAb), aflibercept, or phosphate-buffered saline (PBS). CoNV and opacity were graded on day 10 post-injury. On day 10, corneas were harvested, and blood vessels and fibrosis markers were assessed by immunofluorescence and confocal microscopy. Furthermore, qPCR and Western blot were performed to quantify fibrosis markers.
Results :
Anti-Scg3 hAb treatment significantly reduced both neovascularization (P=0.0002) and opacity scores (P=0.0009) compared to the control group at day 10. Additionally, anti-Scg3 treatment significantly inhibited total blood vessel length (P=0.0029). Aflibercept demonstrated similar high efficacy in reducing neovascularization score (P <0.00001) and total blood vessel length (P=0.0214). However, aflibercept was ineffective in reducing corneal opacity. Anti-Scg3 hAb-treated mice exhibited significantly lowered opacity scores compared to the aflibercept treated group (P=0.0004). Immunostaining confirmed that anti-Scg3 hAb markedly reduced CD31+ blood vessels with efficacy comparable to that of aflibercept treatment. Furthermore, anti-Scg3 hAb, but not aflibercept, markedly reduced the expression of fibronectin and α-SMA expression in alkali-burned corneas.
Conclusions :
These findings suggest that anti-Scg3 hAb has the potential to prevent both CoNV and opacity after alkali burn. Given the disease-targeting property of anti-Scg3 hAb to selectively inhibit pathological angiogenesis and opacity without discernible adverse effects, our results justify further studies to evaluate the efficacy and safety of anti-Scg3 for dual anti-angiogenic and anti-opacity therapy.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.