Freddo T F, Bartels S P, Barsotti M F, Kamm R D
Department of Ophthalmology, Boston University School of Medicine, MA 02118.
Invest Ophthalmol Vis Sci. 1990 Jan;31(1):125-37.
Aqueous fluorophotometric, tracer localization and modeling methods were combined to document the existence of a pathway in the normal rabbit for the diffusion of proteins from the ciliary and iridial process stromas through the iris stroma into the aqueous humor of the anterior chamber. A new custom-conjugated tracer, fluoresceinated horseradish peroxidase (F-HRP), was used. Anesthetized rabbits were injected intravenously with F-HRP (250 mg/kg). In some animals, aqueous fluorophotometric and tracer localization studies were performed on the same eyes. Anterior chamber fluorescence was detected 2-10 min post-injection and rose to concentrations of 0.01-0.05 mg/ml 60 min post-injection. Subsequent tracer localization studies of these eyes revealed that the morphologic components of the blood-aqueous barrier were intact, that is, no leakage of F-HRP from the iris vasculature or across the ciliary epithelium was observed. Separate tracer localization studies were performed to examine the time course of the route(s) by which tracer entered the anterior chamber. These studies revealed a "wave" of tracer that migrated from the ciliary and iridial process stromas, through the iris, and arrived at the anterior iris surface approximately 8 min post-injection. A pharmacokinetic model based on the diffusional pathway was developed to describe the time course of the concentration of plasma macromolecules in the ciliary body, iris and anterior chamber. Model predictions were consistent with aqueous fluorophotometric and tracer localization results. The diffusion model can account for a major fraction of protein entering the aqueous humor of normal rabbit eyes.
将水性荧光光度法、示踪剂定位法和建模方法相结合,以证明在正常兔眼中存在一条途径,蛋白质可通过该途径从睫状体和虹膜基质扩散穿过虹膜基质进入前房房水。使用了一种新的定制共轭示踪剂,即荧光素化辣根过氧化物酶(F-HRP)。对麻醉的兔子静脉注射F-HRP(250mg/kg)。在一些动物中,对同一只眼睛进行了房水荧光光度法和示踪剂定位研究。注射后2-10分钟检测到前房荧光,注射后60分钟荧光浓度升至0.01-0.05mg/ml。随后对这些眼睛进行的示踪剂定位研究表明,血-房水屏障的形态学成分完好无损,即未观察到F-HRP从虹膜血管系统泄漏或穿过睫状体上皮。进行了单独的示踪剂定位研究,以检查示踪剂进入前房的途径的时间进程。这些研究显示,示踪剂形成的“波”从睫状体和虹膜基质迁移,穿过虹膜,在注射后约8分钟到达虹膜前表面。基于扩散途径建立了一个药代动力学模型,以描述睫状体、虹膜和前房中血浆大分子浓度的时间进程。模型预测结果与房水荧光光度法和示踪剂定位结果一致。该扩散模型可以解释进入正常兔眼房水的大部分蛋白质。