Leber遗传性视神经病变与细胞凋亡

Leber's hereditary optic neuropathy and cell apoptosis

Leber遗传性视神经病变(leber'shereditaryopticneuropathy,LHON)是一种严重威胁青少年视功能的不可逆致盲性眼病,发病机制目前尚无统一的认识。以往对其病理机制的研究和假说都集中在酶生物活性的缺陷上,但缺乏足够的证据。Steven发现,LHON表现出来的视神经节细胞的死亡是凋亡,它由Fas启动,被半胱氨酸蛋白酶(caspase)抑制剂阻断,表现出caspase活性及caspase-3分解蛋白质的能力增强,并且细胞Annexin-V染色阳性。11778,3460位点病理性突变增强了细胞对Fas介导的凋亡的敏感性,可能是最直接的原因。这一发现可能揭示LHON的发病机制,也暗示了可以运用抗凋亡药物对其进行治疗。

Leber＇s hereditary optic neuropathy （ LHON ） is a kind of disease which seriously threatens the visual function of the youth and can lead to blindness. The pathogenesis of LHON is not known yet. Most hypotheses for the pathophysiological mechanism of LHON have focused on the possibility of a bioenergetic defect, bur lacking of support- ing. Steven has shown that the retinal ganglion cells＇ death in LHON is apoptosis, which is started by Fas, inhibited by a caspase inhibitor （zVAD-fmk） and can result in the increased DEVDase activity, caspase-3 cleavage and Annexin-V staining. The most straightforward interpretation of these results is that the 11778 and 3460 LHON pathogenic mutations increasing the sensitivity of the cells to apoptotic death mediated through the Fas pathway. This discovery maybe bring the light to the pathogenesis of LHON, and suggest the new therapeutic method.