RESUMEN
Purpose: Intravitreal injection of anti-VEGF antibodies remains the primary therapy for exudative age-related macular degeneration (exAMD), although its efficacy is limited. Previous research has demonstrated that both a loss-of-function mutation of srr and the intravenous injection of a serine racemase inhibitor, L-aspartic acid ß-hydroxamate (L-ABH), significantly inhibit laser-induced choroidal neovascularization (CNV) in mice. Given that L-ABH is a small molecule, this study investigated the effects of L-ABH administered via eye drops on CNV, aiming to develop a noninvasive treatment strategy for exAMD. Methods: CNV models in mice and rhesus macaques were established through laser photocoagulation. Seven monkeys were randomly assigned to receive either saline solution or L-ABH eye drops. Intraperitoneal or intravenous injection of fluorescein characterized CNV in both mice and monkeys. Fluorescein fundus angiography was used to assess leakage, whereas optical coherence tomography measured retinal thickness in the monkeys. Results: L-ABH eye drops significantly reduced fluorescein leakage in laser-injured mice (P < 0.001 compared to saline). In laser-injured rhesus macaques, the average percent changes in leakage areas treated with L-ABH were 2.5% ± 25.8% (P = 0.004) and 1.5% ± 75.7% (P = 0.023 compared to saline solution) on day 14 and day 28, respectively. However, L-ABH eye drops did not significantly affect the number of grade IV laser spots or retinal thickness, whereas bevacizumab did. Conclusions: This study demonstrates the potential efficacy of an SRR inhibitor in two animal models of laser-induced CNV. Translational Relevance: This represents the first investigation into the effects of topical delivery of an SRR inhibitor on CNV.
Asunto(s)
Neovascularización Coroidal , Modelos Animales de Enfermedad , Angiografía con Fluoresceína , Macaca mulatta , Ratones Endogámicos C57BL , Tomografía de Coherencia Óptica , Animales , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/patología , Ratones , Racemasas y Epimerasas/antagonistas & inhibidores , Racemasas y Epimerasas/genética , Racemasas y Epimerasas/metabolismo , Coagulación con Láser/efectos adversos , Soluciones Oftálmicas , Masculino , Coroides/efectos de los fármacos , Coroides/patología , Coroides/diagnóstico por imagen , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/uso terapéutico , Ácidos Hidroxámicos/administración & dosificación , Ácidos Hidroxámicos/farmacología , Ácidos Hidroxámicos/uso terapéuticoRESUMEN
A highly efficient flame retardant and smoke suppression oligomer, oligo(phenylphosphonic dihydroxypropyl silicone oil) (PPSO), was synthesized by a one-step reaction. The chemical structure of PPSO was confirmed by Fourier transform infrared (FTIR), 31P nuclear magnetic resonance (31P NMR), and 29Si nuclear magnetic resonance (29Si NMR). The flame-retardant effect of PPSO on the polycarbonate (PC) matrix was investigated by limiting oxygen index, UL-94 vertical burning test, and cone calorimetry, respectively. The results showed that PC/PPSO composites passed UL-94 V-0 rate testing with only 1.3 wt. % PPSO. Furthermore, the incorporation of PPSO can suppress the release of smoke. The flame-retardant mechanism was also investigated via thermogravimetric analysis-fourier transform infrared spectroscopy (TG-FTIR), field-emission scanning electronic microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy. From the result of pyrolysis gas and char residue, PPSO played a synergistic flame-retardant mechanism including the gas phase and the condensed phase.