Oshitari T, Yamamoto S, Hata N, Roy S
Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Chiba, Japan.
Br J Ophthalmol. 2008 Apr;92(4):552-6. doi: 10.1136/bjo.2007.132308.
Neuronal abnormalities are associated with the pathogenesis of diabetic retinopathy. However, the mechanisms for neuronal cell death in diabetic retinopathy remain unclear.
To determine whether altered expression of Bax, caspase-9 and -3 is associated with degenerative neurons in diabetic retinopathy.
Immunohistochemistry was performed on cryosections obtained from five pairs of normal and five pairs of age-matched diabetic human retinas. Diabetic eyes had no proliferative diabetic retinopathy and no histories of photocoagulation or ocular surgery. In this study, Fluoro-Jade B (FJB) was used as a marker for identification of degenerative neurons.
In diabetic retinas, Bax overexpression coexisted with FJB positive signals in the ganglion cell layer (GCL) compared with very low FJB levels in the normal retina. Increased level of the active forms of caspase-9 and -3 expressions coexisted with FJB positive cells in the GCL of diabetic retinas compared with those in normal retinas.
Upregulation of Bax, caspase-9 and -3 expression was associated with neuronal degeneration in diabetic retinopathy. The mitochondria- and caspase-dependent cell-death pathway may be, in part, associated with neuronal degeneration in diabetic retinas.
神经元异常与糖尿病视网膜病变的发病机制相关。然而,糖尿病视网膜病变中神经元细胞死亡的机制仍不清楚。
确定Bax、半胱天冬酶-9和-3表达的改变是否与糖尿病视网膜病变中的退行性神经元相关。
对取自5对正常人和5对年龄匹配的糖尿病患者的冷冻切片进行免疫组织化学检测。糖尿病患者的眼睛无增殖性糖尿病视网膜病变,且无光凝或眼科手术史。在本研究中,使用Fluoro-Jade B(FJB)作为识别退行性神经元的标志物。
与正常视网膜中极低的FJB水平相比,在糖尿病视网膜中,Bax的过度表达与神经节细胞层(GCL)中的FJB阳性信号共存。与正常视网膜相比,糖尿病视网膜GCL中半胱天冬酶-9和-3活性形式表达水平的增加与FJB阳性细胞共存。
Bax、半胱天冬酶-9和-3表达上调与糖尿病视网膜病变中的神经元变性相关。线粒体和半胱天冬酶依赖性细胞死亡途径可能部分与糖尿病视网膜中的神经元变性有关。