Subconjunctival Injection of Anti-Secretogranin III Mitigates Corneal Damage in Alkali Burn Injury Model

Purpose: Corneal neovascularization (CoNV) following ocular surface injuries can lead to vision loss and are frequently associated with corneal opacity. Current therapies, including anti-vascular endothelial growth factor (VEGF) agents, can reduce CoNV but have potential adverse effects on the corneal surface and do not effectively address opacity. Anti-secretogranin III (anti-Scg3) neutralizing antibodies, developed for disease-targeted intervention of ocular angiogenic diseases, may offer safety advantages. This study aimed to characterize the therapeutic activity of early anti-Scg3 neutralizing antibody administration in reducing the development of CoNV and opacity in a mouse alkali burn injury model and to compare the efficacy with that of the anti-VEGF drug aflibercept. Methods: C57BL/6J mice with induced alkali burns were treated subconjunctivally with anti-Scg3 humanized antibody (hAb), aflibercept, or phosphate-buffered saline (PBS). CoNV and opacity were visually scored on day 10 post-injury. Corneas were harvested for immunofluorescence, quantitative reverse transcription PCR, and proteome profiling to assess angiogenic, and fibrosis associated markers. Results: Early anti-Scg3 hAb treatment significantly reduced the development of CoNV, encompassing both hemangiogenesis and lymphangiogenesis, and markedly decreased corneal opacity compared with the untreated group. In contrast, aflibercept treatment reduced hemangiogenesis to a similar extent but did not significantly affect lymphangiogenesis or opacity. Conclusions: A single subconjunctival injection of anti-Scg3 hAb administered immediately following alkali burn injury effectively reduced the development of CoNV and corneal opacity under the conditions evaluated in this study. These findings support further investigation of anti-Scg3 hAb as an early intervention for acute corneal injury.