Cruysberg Lars P J, Nuijts Rudy M M A, Geroski Dayle H, Gilbert Jake A, Hendrikse Fred, Edelhauser Henry F
Department of Ophthalmology, Emory University, Atlanta, GA 30322, USA.
Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3790-4. doi: 10.1167/iovs.04-1414.
To evaluate the effects of intraocular pressure on the permeability of the human sclera to high-molecular-weight compounds.
Human transscleral permeability to FITC-albumin (70 kDa) and 70-kDa and 150-kDa FITC-dextran was determined at transscleral pressures from 0 to 60 mm Hg. For each compound at each pressure, six to eight experiments were performed. Scleral sections were mounted in a two-compartment perfusion chamber. Temperature was maintained at 37 degrees C. Fractions of choroidal perfusate were collected, and fluorescence was measured with a spectrofluorometer. From these data, scleral permeability K(trans) (in centimeters per second) was calculated.
Permeability to FITC-albumin was decreased by approximately one half when pressure was elevated from 0 to 30 mm Hg (P < 0.05). No significant differences in permeability to 70-kDa FITC-dextran were observed at pressures from 0 to 60 mm Hg. Permeability to 150-kDa FITC-dextran decreased by a little more than one half when transscleral pressure was raised from 0 to 15 mm Hg and was approximately 10 times lower at 60 mm Hg than at 0 mm Hg (P < 0.01).
Human sclera was permeable to compounds with a molecular weight of up to 150 kDa at transscleral pressures ranging from 0 to 60 mm Hg. Transscleral diffusion was relatively unaffected by the pressure gradient, although for 150-kDa FITC-dextran at 60 mm Hg a 10-fold decrease was observed compared with that at 0 mm Hg. These experiments suggest that high-molecular-weight compounds (e.g., immunoglobulins and oligonucleotides) could be effectively delivered transsclerally to the intraocular tissues under circumstances of physiological or elevated intraocular pressure.
评估眼压对人巩膜对高分子量化合物通透性的影响。
在0至60毫米汞柱的经巩膜压力下，测定人经巩膜对异硫氰酸荧光素标记的白蛋白（70 kDa）以及70 kDa和150 kDa异硫氰酸荧光素标记的葡聚糖的通透性。对于每种化合物在每个压力下，进行六至八次实验。将巩膜切片安装在双室灌注室中。温度维持在37摄氏度。收集脉络膜灌注液的馏分，并用荧光分光光度计测量荧光。根据这些数据，计算巩膜通透性K(trans)（以厘米每秒为单位）。
当压力从0升高至30毫米汞柱时，对异硫氰酸荧光素标记的白蛋白的通透性降低了约一半（P < 0.05）。在0至60毫米汞柱的压力下，未观察到对70 kDa异硫氰酸荧光素标记的葡聚糖的通透性有显著差异。当经巩膜压力从0升高至15毫米汞柱时，对150 kDa异硫氰酸荧光素标记的葡聚糖的通透性降低了略超过一半，并且在60毫米汞柱时比在0毫米汞柱时低约10倍（P < 0.01）。
在0至60毫米汞柱的经巩膜压力范围内，人巩膜对分子量高达150 kDa的化合物具有通透性。经巩膜扩散相对不受压力梯度的影响，尽管对于60毫米汞柱下的150 kDa异硫氰酸荧光素标记的葡聚糖，与0毫米汞柱时相比观察到降低了10倍。这些实验表明，在生理眼压或眼压升高的情况下，高分子量化合物（例如免疫球蛋白和寡核苷酸）可以有效地经巩膜递送至眼内组织。
