El Bradey Mohammed, Cheng Lingyun, Bartsch Dirk-Uwe, Appelt Krzystof, Rodanant Nuttawut, Bergeron-Lynn Germaine, Freeman William R
University of California, San Diego, Jacobs Retina Center, and Shiley Eye Center, La Jolla, CA, USA.
J Ocul Pharmacol Ther. 2004 Jun;20(3):217-36. doi: 10.1089/1080768041223657.
AG3340 (prinomastat) is a nonpeptidic, small-molecular-weight, synthetic matrix metalloproteinase inhibitor (MMPI) with selective inhibitory action of MMP-2, MMP-9, MMP-3, and MT-MMP1. We evaluated AG3340 injected intravitreally to treat choroidal neovascularization in a laser induced rat CNV model.
In the pretreatment group, the drug was injected the same day after induction of choroidal neovascularization by diode laser. In the treatment group, the drug was injected 2 weeks after induction of choroidal neovascularization (CNV). Fluorescein and indocyanine green angiography were performed to evaluate CNV. ERG recordings and histology were performed to assess toxicity and the CNV lesions.
When used at the time of CNV induction, 62.8% of lesions in control versus 22.8% of the laser lesions in treated eyes developed CNV (p < 0.0001). The invading fibrovascular complex was thicker in the control eyes than that in the treated eyes. No signs of toxicity were detected. When used to treat established CNV, the percentage of leakage in treated and control eyes were 54.1% and 58.9% respectively (p > 0.05). Prinomastat was effective when given at the time of induction of CNV in the rat model. Administration of prinomastat 2 weeks after laser induction did not show efficacy.
Prinomastat was active in the earliest stages of experimental CNV. It might be best used in combination with photodynamic therapy to inhibit recurrence of CNV from temporarily closed new vessels.
AG3340（普林司他）是一种非肽类、小分子合成基质金属蛋白酶抑制剂（MMPI），对基质金属蛋白酶-2、基质金属蛋白酶-9、基质金属蛋白酶-3和膜型基质金属蛋白酶-1具有选择性抑制作用。我们评估了玻璃体腔内注射AG3340对激光诱导的大鼠脉络膜新生血管模型中脉络膜新生血管的治疗效果。
在预处理组中，在二极管激光诱导脉络膜新生血管形成后的同一天注射药物。在治疗组中，在脉络膜新生血管形成（CNV）诱导后2周注射药物。进行荧光素和吲哚菁绿血管造影以评估CNV。进行视网膜电图记录和组织学检查以评估毒性和CNV病变。
在CNV诱导时使用，对照组62.8%的病变出现CNV，而治疗组激光诱导的病变中出现CNV的比例为22.8%（p<0.0001）。对照组眼中侵入的纤维血管复合体比治疗组眼中的更厚。未检测到毒性迹象。用于治疗已形成的CNV时，治疗组和对照组眼中渗漏的百分比分别为54.1%和58.9%（p>0.05）。在大鼠模型中，CNV诱导时给予普林司他有效。激光诱导后2周给予普林司他未显示出疗效。
普林司他在实验性CNV的最早阶段具有活性。它可能最适合与光动力疗法联合使用，以抑制暂时封闭的新血管中CNV的复发。
