Publication Date
4-19-2022
Journal
Frontiers in Bioscience
DOI
10.31083/j.fbl2704130
PMID
35468689
PMCID
PMC9201993
PubMedCentral® Posted Date
4-19-2023
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Animals, Humans, Infant, Newborn, Intravitreal Injections, Mice, Mice, Inbred C57BL, Neovascularization, Pathologic, Oxygen, Retinopathy of Prematurity, Vascular Endothelial Growth Factor A, Retinopathy of prematurity, oxygen-induced retinopathy, secretogranin III, Scg3, pathological angiogenesis, physiological angiogenesis, targeted anti-angiogenic therapy
Abstract
BACKGROUND: To circumvent possible systemic side effects, anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) for ocular neovascular diseases in adults are approved only for intravitreal administration. However, intravitreal injection itself can elicit injection-related adverse effects, and premature eyes of infants with retinopathy of prematurity (ROP) may be particularly susceptible to intravitreal injection. Therefore, an unmet clinical need is to develop safe systemic anti-angiogenic therapies for ROP. We recently reported that secretogranin III (Scg3) is a disease-restricted angiogenic factor and that systemic anti-Scg3 mAb alleviates ROP in animal models with minimal side effects on developing eyes and organs. The aim of this study is to investigate the safety and efficacy of a humanized anti-Scg3 antibody via systemic administration.
METHODS: We analyzed the safety and efficacy of a humanized anti-Scg3 antibody Fab fragment (hFab) delivered by intraperitoneal injection in oxygen-induced retinopathy (OIR) mice, a surrogate model of ROP.
RESULTS: The results showed that systemic anti-Scg3 hFab effectively alleviated pathological retinal neovascularization in OIR mice with similar efficacy to the anti-VEGF drug aflibercept. Systemic aflibercept conferred significant adverse side effects in neonatal mice, including reduced body weight, abnormalities in retinal and renal development, and retarded physiological neovascularization, whereas systemic anti-Scg3 hFab elicited no such side effects.
CONCLUSIONS: The findings suggest that systemic anti-Scg3 hFab is a safe and effective therapy for OIR and support further development for ROP treatment.