Acevedo-Jake Amanda, Shi Siyu, Siddiqui Zain, Sanyal Sreya, Schur Rebecca, Kaja Simon, Yuan Alex, Kumar Vivek A
Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA.
Bioengineering (Basel). 2021 Nov 23;8(12):190. doi: 10.3390/bioengineering8120190.
Pro-angiogenic and anti-angiogenic peptide hydrogels were evaluated against the standard of care wet age-related macular degeneration (AMD) therapy, Aflibercept (Eylea). AMD was modeled in rats (laser-induced choroidal neovascularization (CNV) model), where the contralateral eye served as the control. After administration of therapeutics, vasculature was monitored for 14 days to evaluate leakiness. Rats were treated with either a low or high concentration of anti-angiogenic peptide hydrogel (0.02 wt% 8 rats, 0.2 wt% 6 rats), or a pro-angiogenic peptide hydrogel (1.0 wt% 7 rats). As controls, six rats were treated with commercially available Aflibercept and six with sucrose solution (vehicle control). Post lasering, efficacy was determined over 14 days via fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). Before and after treatment, the average areas of vascular leak per lesion were evaluated as well as the overall vessel leakiness. Unexpectedly, treatment with pro-angiogenic peptide hydrogel showed significant, immediate improvement in reducing vascular leak; in the short term, the pro-angiogenic peptide performed better than anti-angiogenic peptide hydrogel and was comparable to Aflibercept. After 14 days, both the pro-angiogenic and anti-angiogenic peptide hydrogels show a trend of improvement, comparable to Aflibercept. Based on our results, both anti-angiogenic and pro-angiogenic peptide hydrogels may prove good therapeutics in the future to treat wet AMD over a longer-term treatment period.
针对湿性年龄相关性黄斑变性（AMD）的标准治疗药物阿柏西普（Eylea），对促血管生成和抗血管生成肽水凝胶进行了评估。在大鼠中建立AMD模型（激光诱导脉络膜新生血管（CNV）模型），对侧眼作为对照。给药后，监测血管系统14天以评估渗漏情况。大鼠分别接受低浓度或高浓度的抗血管生成肽水凝胶（0.02 wt%，8只大鼠；0.2 wt%，6只大鼠）或促血管生成肽水凝胶（1.0 wt%，7只大鼠）治疗。作为对照，6只大鼠接受市售阿柏西普治疗，6只大鼠接受蔗糖溶液（赋形剂对照）治疗。激光照射后，通过荧光素血管造影（FA）和光谱域光学相干断层扫描（SD-OCT）在14天内确定疗效。治疗前后，评估每个病变的血管渗漏平均面积以及总体血管渗漏情况。出乎意料的是，促血管生成肽水凝胶治疗在减少血管渗漏方面显示出显著的即时改善；短期内，促血管生成肽的效果优于抗血管生成肽水凝胶，且与阿柏西普相当。14天后，促血管生成和抗血管生成肽水凝胶均显示出改善趋势，与阿柏西普相当。根据我们的结果，抗血管生成和促血管生成肽水凝胶在未来长期治疗湿性AMD方面可能都将被证明是良好的治疗药物。
