Stitt Alan W, Graham Donna, Gardiner Tom A
Ophthalmic Research Centre, Queen's University Belfast, Institute of Clinical Sciences, Royal Victoria Hospital, Belfast, Northern Ireland, UK.
Mol Vis. 2004 Jun 28;10:432-8.
Perforation injury to the eye can protect against retinal degeneration and pigment epithelial derived factor (PEDF) may play a role in this neuro-protective effect. PEDF has also been shown to possess potent anti-angiogenic properties. The current study has investigated a possible anti-angiogenic effect of penetrating ocular injury in a murine model of oxygen induced proliferative retinopathy (OIR) and determined if such a procedure alters PEDF expression in the retina.
OIR was produced by exposure of neonatal mice to 75% oxygen between postnatal days 7 and 12 (P7-P12). Mice were separated into various groups, with one group receiving a penetrating injury in a single eye. Pre-retinal neovascularization and intra-retinal ischaemia was quantified at P17 and PEDF protein expression was determined using immunofluorescence in retinal flatmounts and sections. PEDF mRNA was quantified using real-time RT-PCR.
Punctured eyes showed less pre-retinal neovascularization at P17 when compared to the non-punctured eyes (p<0.001) although there was no effect on retinal ischaemia. PEDF immunreactivity was strongest in the ganglion cells of the retina, and intensity increased in punctured eyes at P13. There was more immunoreactive PEDF in ganglion cells adjacent to retinal venules than arterioles. At P13, retinal PEDF mRNA was also increased in punctured eyes compared to non-punctured controls (p<0.05), although there was no differential at P17.
Penetrating ocular injury suppresses retinal neovascularization and modulates expression of PEDF. These findings have implications for intra-vitreal delivery of angiostatic agents since ocular perforation may provoke an acute, endogenous anti-angiogenic response that should be taken into account.
眼部穿孔伤可预防视网膜变性,色素上皮衍生因子(PEDF)可能在此神经保护作用中发挥作用。PEDF还显示出具有强大的抗血管生成特性。本研究在氧诱导增生性视网膜病变(OIR)的小鼠模型中研究了穿透性眼外伤可能的抗血管生成作用,并确定该操作是否会改变视网膜中PEDF的表达。
通过在出生后第7天至12天(P7 - P12)将新生小鼠暴露于75%氧气中来诱导OIR。将小鼠分为不同组,其中一组单眼接受穿透性损伤。在P17时对视网膜前新生血管形成和视网膜内缺血进行定量,并使用视网膜平铺片和切片中的免疫荧光法测定PEDF蛋白表达。使用实时RT - PCR对PEDF mRNA进行定量。
与未穿孔的眼睛相比,穿孔的眼睛在P17时视网膜前新生血管形成较少(p<0.001),尽管对视网膜缺血没有影响。PEDF免疫反应性在视网膜神经节细胞中最强,在P13时穿孔眼睛中的强度增加。与视网膜小动脉相邻的神经节细胞中,免疫反应性PEDF在视网膜小静脉周围更多。在P13时,与未穿孔对照相比,穿孔眼睛中的视网膜PEDF mRNA也增加(p<0.05),尽管在P17时没有差异。
穿透性眼外伤可抑制视网膜新生血管形成并调节PEDF的表达。这些发现对于玻璃体内递送血管生成抑制剂具有重要意义,因为眼部穿孔可能引发急性内源性抗血管生成反应,应予以考虑。