Renno Reem Z, Youssri Ayman I, Michaud Norman, Gragoudas Evangelos S, Miller Joan W
Angiogenesis Laboratory, Retina Research Institute, Massachusetts Eye and Ear Infirmary, 245 Charles Street, Boston, MA 02114, USA.
Invest Ophthalmol Vis Sci. 2002 May;43(5):1574-80.
To investigate the expression of pigment epithelium-derived factor (PEDF) in the rat laser-injury model of choroidal neovascularization (CNV).
Retinas were immunostained for PEDF at different times (1, 2, and 3 weeks) after laser injury. Levels of PEDF protein in the vitreous at 1, 3, 7, 14, and 28 days after laser injury were also assayed by Western blot.
Protein levels of PEDF in the vitreous were increased during the first 7 days after CNV induction. Immunostaining for PEDF was observed throughout normal nonlasered control retinas, sham-lasered retinas, and areas remote to laser lesions, which were generally more intense in the outer nuclear layer (ONL) and less intense in the internal nuclear layer (INL). Decreased expression of PEDF was observed in flanking areas adjacent to the injury site and was confined mainly to the ONL. In the injury sites, immunostaining within the ONL was either absent or decreased for up to 3 weeks after laser injury (the duration of the study). Preadsorption of the anti-PEDF antibody with the immunizing peptide blocked specific labeling in the retina.
These results demonstrate an inverse correlation of expression of PEDF and formation of CNV in the experimental model and suggest that decreased expression of PEDF plays a permissive role in the formation of CNV. PEDF analogues may be a reasonable treatment strategy for CNV.
研究色素上皮衍生因子(PEDF)在大鼠脉络膜新生血管(CNV)激光损伤模型中的表达。
在激光损伤后的不同时间点(1、2和3周)对视网膜进行PEDF免疫染色。还通过蛋白质印迹法检测激光损伤后1、3、7、14和28天玻璃体中PEDF蛋白的水平。
在诱导CNV后的前7天,玻璃体中PEDF的蛋白水平升高。在整个正常未激光照射的对照视网膜、假激光照射的视网膜以及远离激光损伤部位均观察到PEDF免疫染色,其在外核层(ONL)通常更强,在内核层(INL)较弱。在损伤部位相邻的侧翼区域观察到PEDF表达降低,且主要局限于ONL。在损伤部位,激光损伤后长达3周(研究持续时间),ONL内的免疫染色缺失或减少。用免疫肽预吸附抗PEDF抗体可阻断视网膜中的特异性标记。
这些结果表明在实验模型中PEDF表达与CNV形成呈负相关,并提示PEDF表达降低在CNV形成中起促进作用。PEDF类似物可能是治疗CNV的合理策略。