Vähätupa Maria, Salonen Niklas, Uusitalo-Järvinen Hannele, Järvinen Tero A H
Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland.
Eye Centre & Department of Orthopedics & Traumatology, Tampere University Hospital, 33520 Tampere, Finland.
Pharmaceutics. 2021 Nov 15;13(11):1932. doi: 10.3390/pharmaceutics13111932.
Pathological angiogenesis is the hallmark of ischemic retinal diseases among them retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR). Oxygen-induced retinopathy (OIR) is a pure hypoxia-driven angiogenesis model and a widely used model for ischemic retinopathies. We explored whether the vascular homing peptide CAR (CARSKNKDC) which recognizes angiogenic blood vessels can be used to target the retina in OIR. We were able to demonstrate that the systemically administered CAR vascular homing peptide homed selectively to the preretinal neovessels in OIR. As a cell and tissue-penetrating peptide, CAR also penetrated into the retina. Hyperoxia used to induce OIR in the retina also causes bronchopulmonary dysplasia in the lungs. We showed that the CAR peptide is not targeted to the lungs in normal mice but is targeted to the lungs after hyperoxia-/hypoxia-treatment of the animals. The site-specific delivery of the CAR peptide to the pathologic retinal vasculature and the penetration of the retinal tissue may offer new opportunities for treating retinopathies more selectively and with less side effects.
病理性血管生成是缺血性视网膜疾病的标志，其中包括早产儿视网膜病变（ROP）和增殖性糖尿病视网膜病变（PDR）。氧诱导性视网膜病变（OIR）是一种纯粹由缺氧驱动的血管生成模型，也是缺血性视网膜病变广泛使用的模型。我们探究了识别血管生成血管的血管归巢肽CAR（CARSKNKDC）是否可用于在OIR中靶向视网膜。我们能够证明，全身给药的CAR血管归巢肽选择性归巢至OIR中的视网膜前新生血管。作为一种细胞和组织穿透肽，CAR也可穿透进入视网膜。用于在视网膜中诱导OIR的高氧也会导致肺部支气管肺发育不良。我们表明，CAR肽在正常小鼠中不会靶向肺部，但在对动物进行高氧/低氧处理后会靶向肺部。CAR肽向病理性视网膜血管系统的位点特异性递送以及视网膜组织的穿透可能为更具选择性且副作用更少地治疗视网膜病变提供新机会。
