PDF(Pubmed)
Abstract：
UNASSIGNED: To evaluate the therapeutic benefit of a novel peptide, ALM201, in ocular pathologic vascularization.
UNASSIGNED: Experimental study in mouse, rat, and rabbit animal models.
UNASSIGNED: Ten-week-old Lister Hooded male rats, 8-week-old Brown Norway male rats, 9-day-old C57BL/6J mice, and 12-month-old New Zealand male rabbits.
UNASSIGNED: Corneal vascularization was scored for vessel density and vessel distance to suture in a rat corneal suture model. Ocular penetration and biodistribution were evaluated by matrix-assisted laser desorption/ionization mass spectrometry imaging after topical ALM201 application to rabbit eyes. A mouse choroidal sprouting assay, with aflibercept as positive control, was used to evaluate choroidal neovascularization (CNV) in the posterior segment tissue. Efficacy of topical ALM201 was assessed using a rat laser CNV model of neovascular age-related macular degeneration.
UNASSIGNED: Clinical scoring and histologic analysis of vascularized corneas, sprouting area, lesion size, and vessel leakiness in posterior segments.
UNASSIGNED: Assessment of ALM201 treatment in the rat corneal suture model showed a significant decrease in vessel density (P = 0.0065) and vessel distance to suture (P = 0.021) compared with vehicle control (phosphate-buffered saline [PBS]). Infiltration of inflammatory cells into the corneal stroma also was reduced significantly compared with PBS (724.5 ± 122 cells/mm2 vs. 1837 ± 195.9 cells/mm2, respectively; P = 0.0029). Biodistribution in rabbit eyes confirmed ALM201 bioavailability in anterior and posterior ocular segments 1 hour after topical instillation. ALM201 treatment significantly suppressed choroid vessel sprouting when compared with PBS treatment (44.5 ± 14.31 pixels vs. 120.9 ± 33.37 pixels, respectively; P = 0.04) and was not inferior to aflibercept (65.63 ± 11.86 pixels; P = 0.7459). Furthermore, topical ALM201 significantly improved vessel leakiness (leakage scores: 2.1 ± 0.7 vs. 2.9 ± 0.1; P = 0.0274) and lesion size (144,729 ± 33,239 μm3 vs. 187,923 ± 28,575 μm3; P = 0.03) in the rat laser CNV model when compared with topical PBS vehicle.
UNASSIGNED: ALM201 is a promising novel molecule with anti-inflammatory and antivascularization activity and is a strong candidate to meet the clinical need of a new, topically delivered therapeutic agent for treating inflammation and pathologic vascularization in the anterior and posterior segments of the eye.
UNASSIGNED: Experimental study in mouse, rat, and rabbit animal models.
UNASSIGNED: Ten-week-old Lister Hooded male rats, 8-week-old Brown Norway male rats, 9-day-old C57BL/6J mice, and 12-month-old New Zealand male rabbits.
UNASSIGNED: Corneal vascularization was scored for vessel density and vessel distance to suture in a rat corneal suture model. Ocular penetration and biodistribution were evaluated by matrix-assisted laser desorption/ionization mass spectrometry imaging after topical ALM201 application to rabbit eyes. A mouse choroidal sprouting assay, with aflibercept as positive control, was used to evaluate choroidal neovascularization (CNV) in the posterior segment tissue. Efficacy of topical ALM201 was assessed using a rat laser CNV model of neovascular age-related macular degeneration.
UNASSIGNED: Clinical scoring and histologic analysis of vascularized corneas, sprouting area, lesion size, and vessel leakiness in posterior segments.
UNASSIGNED: Assessment of ALM201 treatment in the rat corneal suture model showed a significant decrease in vessel density (P = 0.0065) and vessel distance to suture (P = 0.021) compared with vehicle control (phosphate-buffered saline [PBS]). Infiltration of inflammatory cells into the corneal stroma also was reduced significantly compared with PBS (724.5 ± 122 cells/mm2 vs. 1837 ± 195.9 cells/mm2, respectively; P = 0.0029). Biodistribution in rabbit eyes confirmed ALM201 bioavailability in anterior and posterior ocular segments 1 hour after topical instillation. ALM201 treatment significantly suppressed choroid vessel sprouting when compared with PBS treatment (44.5 ± 14.31 pixels vs. 120.9 ± 33.37 pixels, respectively; P = 0.04) and was not inferior to aflibercept (65.63 ± 11.86 pixels; P = 0.7459). Furthermore, topical ALM201 significantly improved vessel leakiness (leakage scores: 2.1 ± 0.7 vs. 2.9 ± 0.1; P = 0.0274) and lesion size (144,729 ± 33,239 μm3 vs. 187,923 ± 28,575 μm3; P = 0.03) in the rat laser CNV model when compared with topical PBS vehicle.
UNASSIGNED: ALM201 is a promising novel molecule with anti-inflammatory and antivascularization activity and is a strong candidate to meet the clinical need of a new, topically delivered therapeutic agent for treating inflammation and pathologic vascularization in the anterior and posterior segments of the eye.
摘要：
未经批准：为了评估一种新型肽的治疗益处，ALM201，在眼部病理性血管化中。
未经评估：小鼠实验研究，rat,和兔子动物模型。
未经授权：10周大的李斯特带帽雄性大鼠，8周大的棕色挪威雄性老鼠，9日龄C57BL/6J小鼠,和12个月大的新西兰公兔.
未经证实：在大鼠角膜缝合模型中，对角膜血管形成进行血管密度和血管距离评分。将ALM201局部应用于兔眼后，通过基质辅助激光解吸/电离质谱成像评估眼部渗透和生物分布。小鼠脉络膜发芽试验，以阿柏西普作为阳性对照，用于评估脉络膜后段组织中的新生血管(CNV)。使用新生血管性年龄相关性黄斑变性的大鼠激光CNV模型评估局部ALM201的功效。
未经评估：血管化角膜的临床评分和组织学分析，发芽面积,病变大小,和后段血管渗漏。
UNASSIGNED:大鼠角膜缝合模型中ALM201处理的评估显示,与媒介物对照(磷酸盐缓冲盐水[PBS])相比,血管密度(P=0.0065)和血管到缝合的距离(P=0.021)显著降低。与PBS相比，炎性细胞向角膜基质的浸润也显着减少（724.5±122个细胞/mm2vs.分别为1837±195.9细胞/mm2;P=0.0029)。兔眼中的生物分布证实了局部滴注后1小时ALM201在前眼和后眼节中的生物利用度。与PBS治疗相比，ALM201治疗可显着抑制脉络膜血管发芽（44.5±14.31像素与120.9±33.37像素，分别；P=0.04）并且不低于阿柏西普（65.63±11.86像素；P=0.7459）。此外，局部ALM201显着改善了血管渗漏（渗漏评分：2.1±0.7vs.2.9±0.1；P=0.0274）和病变大小（144,729±33,239μm3vs.与局部PBS载体相比，大鼠激光CNV模型中的187,923±28,575μm3；P=0.03）。
UNASSIGNED：ALM201是一种具有抗炎和抗血管形成活性的新型分子，是满足新型，局部递送的治疗剂,用于治疗眼睛的前段和后段中的炎症和病理性血管形成。
未经评估：小鼠实验研究，rat,和兔子动物模型。
未经授权：10周大的李斯特带帽雄性大鼠，8周大的棕色挪威雄性老鼠，9日龄C57BL/6J小鼠,和12个月大的新西兰公兔.
未经证实：在大鼠角膜缝合模型中，对角膜血管形成进行血管密度和血管距离评分。将ALM201局部应用于兔眼后，通过基质辅助激光解吸/电离质谱成像评估眼部渗透和生物分布。小鼠脉络膜发芽试验，以阿柏西普作为阳性对照，用于评估脉络膜后段组织中的新生血管(CNV)。使用新生血管性年龄相关性黄斑变性的大鼠激光CNV模型评估局部ALM201的功效。
未经评估：血管化角膜的临床评分和组织学分析，发芽面积,病变大小,和后段血管渗漏。
UNASSIGNED:大鼠角膜缝合模型中ALM201处理的评估显示,与媒介物对照(磷酸盐缓冲盐水[PBS])相比,血管密度(P=0.0065)和血管到缝合的距离(P=0.021)显著降低。与PBS相比，炎性细胞向角膜基质的浸润也显着减少（724.5±122个细胞/mm2vs.分别为1837±195.9细胞/mm2;P=0.0029)。兔眼中的生物分布证实了局部滴注后1小时ALM201在前眼和后眼节中的生物利用度。与PBS治疗相比，ALM201治疗可显着抑制脉络膜血管发芽（44.5±14.31像素与120.9±33.37像素，分别；P=0.04）并且不低于阿柏西普（65.63±11.86像素；P=0.7459）。此外，局部ALM201显着改善了血管渗漏（渗漏评分：2.1±0.7vs.2.9±0.1；P=0.0274）和病变大小（144,729±33,239μm3vs.与局部PBS载体相比，大鼠激光CNV模型中的187,923±28,575μm3；P=0.03）。
UNASSIGNED：ALM201是一种具有抗炎和抗血管形成活性的新型分子，是满足新型，局部递送的治疗剂,用于治疗眼睛的前段和后段中的炎症和病理性血管形成。
