Biochemistry Department, Biosciences Research Institute, University College Cork, Cork, Ireland.
Exp Cell Res. 2012 Jul 1;318(11):1278-84. doi: 10.1016/j.yexcr.2012.02.003. Epub 2012 Feb 13.
There is an urgent need for therapies for retinal diseases; retinitis pigmentosa sufferers have no treatment options available and those targeted at other retinopathies have shown limited effectiveness. The process of programmed cell death or apoptosis although complex, remains a possible target for the treatment of retinal diseases. Having identified apoptosis in the vertebrate retina in populations of immature neurons as an essential part of development it was proposed that re-activation of these developmental cell death pathways might provide insight into the death mechanisms operating in retinal diseases. However, the discovery that numerous factors initiate and mediate the apoptotic cascade in mature photoreceptors has resulted in a relatively untargeted approach to examining and arresting apoptosis in the retina. In the last 5 years, mouse models have been treated with a diverse range of drugs or factors including anti-oxidants, growth factors, steroid hormones, calcium/calpain inhibitors and tetracycline antibiotics. Therefore to draw a unifying theme from these broad research areas is challenging. However, this review focusses on two targets which are currently under investigation, reactive oxygen species and mammalian target of rapamycin, drawing together the common themes of these research areas.
目前非常需要针对视网膜疾病的疗法;色素性视网膜炎患者没有可用的治疗方法,而针对其他视网膜病变的治疗方法效果有限。程序性细胞死亡或细胞凋亡的过程虽然复杂,但仍然是治疗视网膜疾病的一个可能靶点。已经在未成熟神经元群体中确定了脊椎动物视网膜中的细胞凋亡是发育的一个必要部分,因此有人提出重新激活这些发育性细胞死亡途径可能有助于深入了解在视网膜疾病中起作用的死亡机制。然而,大量的研究发现许多因素在成熟光感受器中引发和介导细胞凋亡级联反应,这导致了对视网膜细胞凋亡的检查和阻断相对没有针对性。在过去的 5 年中,已经使用了各种药物或因子(包括抗氧化剂、生长因子、类固醇激素、钙/钙蛋白酶抑制剂和四环素抗生素)来治疗小鼠模型。因此,从这些广泛的研究领域中得出一个统一的主题是具有挑战性的。然而,这篇综述集中讨论了目前正在研究的两个靶点,即活性氧和哺乳动物雷帕霉素靶蛋白,将这些研究领域的共同主题汇集在一起。