Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Eye (Lond). 2010 May;24(5):918-26. doi: 10.1038/eye.2009.173. Epub 2009 Sep 11.
To investigate the possible roles of retinal photoreceptors in macular oedema and retinal angiogenesis with particular reference to the mode of action of laser therapy.
(i) Studies in rats made hypoxic for 2 h by administering an oxygen/nitrogen mixture of reduced oxygen content, and growth factors determined by RT-PCR, western blotting, and immunohistochemistry. Assessment of blood-retinal barrier integrity using fluorescent and electron-dense tracers. (ii) Studies in pigs with one retina made hypoxic by selective embolisation of the retinal capillary circulation with fluorescent microspheres. (iii) Assessment of laser therapy in selected cases of retinal neovascularisation indicating a role for photoreceptors.
In the hypoxic retina, angiogenic and vascular permeability factors such as vascular endothelial growth factor (VEGF), nitric oxide synthases (NOSs), and insulin-like growth factor-1 are upregulated in retinal astrocytes and Müller cells but are also present in large amount in the photoreceptors. Hypoxia-inducible factor-1 (HIF-1) is upregulated in retinal glial cells but not in the photoreceptors, suggesting that growth factors in the photoreceptors may not have been generated there. The tracer dye, rhodium isothiocyanate, leaking from an abnormally permeable inner blood-retinal barrier in the hypoxic retina accumulates in the photoreceptors.
The results indicate that laser treatment of macular oedema or retinal neovascularisation may obtain its effect not only by improving oxygen availability in the inner retina, but also by reducing the load of angiogenic/permeability factors that accumulate in the photoreceptors in hypoxic/ischaemic conditions.
探讨视网膜光感受器在黄斑水肿和视网膜血管生成中的可能作用,特别关注激光治疗的作用模式。
(i)通过给予低氧含量的氧/氮混合物使大鼠缺氧 2 小时,通过 RT-PCR、western 印迹和免疫组织化学测定生长因子。使用荧光和电子致密示踪剂评估血视网膜屏障的完整性。(ii)通过荧光微球选择性栓塞视网膜毛细血管循环使猪的一只视网膜缺氧的研究。(iii)评估激光治疗在提示光感受器作用的视网膜新生血管形成的选定病例中的应用。
在缺氧的视网膜中,血管内皮生长因子(VEGF)、一氧化氮合酶(NOSs)和胰岛素样生长因子-1 等血管生成和血管通透性因子在视网膜星形胶质细胞和 Müller 细胞中上调,但在光感受器中也大量存在。缺氧诱导因子-1(HIF-1)在视网膜神经胶质细胞中上调,但不在光感受器中上调,表明光感受器中的生长因子可能不是在那里产生的。示踪染料异硫氰酸罗丹明从缺氧视网膜中异常通透性的内血视网膜屏障漏出,积聚在光感受器中。
结果表明,黄斑水肿或视网膜新生血管形成的激光治疗不仅可以通过改善内视网膜的氧气供应,而且可以通过减少在缺氧/缺血条件下积聚在光感受器中的血管生成/通透性因子的负荷来获得其效果。