Ren Gaoying, Adamus Grazyna
Neurological Sciences Institute, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
J Autoimmun. 2004 Sep;23(2):161-7. doi: 10.1016/j.jaut.2004.06.003.
Autoantibodies against alpha-enolase are often associated with visual loss in patients with autoimmune retinopathy. Anti-recoverin autoantibodies have been the most extensively studied for their pathologic association with cancer-associated retinopathy (CAR). It has been shown that anti-recoverin antibodies penetrate retinal layers corresponding to the cellular location of recoverin and cause the death of photoreceptors and bipolar cells. However, the pathogenic effects of anti-alpha-enolase antibodies have not been studied. In this study, we tested the labeling and apoptotic effects of such autoantibodies on retinal cells. Serum antibodies against alpha-enolase from patients with autoimmune retinopathy were tested ex vivo and in vivo in Sprague-Dawley rats. Autoantibodies to alpha-enolase specifically labeled the retinal ganglion cells and inner nuclear layer cells. Using ex vivo experiments and intravitreal injections, we observed that antibodies were capable of penetrating retinal tissue to target ganglion cell and inner nuclear layers and, consequently, were able to induce cell death through an apoptotic process. The apoptotic nuclei detected by a DNA fragmentation assay and caspase 3-positive cells were co-localized in the ganglion cell layer and inner nuclear layer. The results showed that antibodies against alpha-enolase target antigens in these layers and induce the apoptotic death of sensitive cells. Rat retinal explants and the intravitreal injection of antibodies provide us with a good model to identify antibody pathogenic targets in the retina. Such identification may help explain the complex of clinical symptoms for autoimmune retinopathy mediated by autoantibody and may help guide treatment strategies.
针对α-烯醇化酶的自身抗体常与自身免疫性视网膜病变患者的视力丧失相关。抗视黄醛结合蛋白自身抗体因其与癌症相关性视网膜病变（CAR）的病理关联而得到了最广泛的研究。已经表明，抗视黄醛结合蛋白抗体穿透与视黄醛结合蛋白细胞定位相对应的视网膜各层，并导致光感受器和双极细胞死亡。然而，抗α-烯醇化酶抗体的致病作用尚未得到研究。在本研究中，我们测试了此类自身抗体对视网膜细胞的标记和凋亡作用。在Sprague-Dawley大鼠体内和体外测试了自身免疫性视网膜病变患者血清中针对α-烯醇化酶的抗体。抗α-烯醇化酶自身抗体特异性标记视网膜神经节细胞和内核层细胞。通过体外实验和玻璃体内注射，我们观察到抗体能够穿透视网膜组织靶向神经节细胞层和内核层，因此能够通过凋亡过程诱导细胞死亡。通过DNA片段化分析检测到的凋亡细胞核和半胱天冬酶3阳性细胞在神经节细胞层和内核层中共定位。结果表明，抗α-烯醇化酶抗体靶向这些层中的抗原并诱导敏感细胞的凋亡死亡。大鼠视网膜外植体和抗体的玻璃体内注射为我们提供了一个识别视网膜中抗体致病靶点的良好模型。这种识别可能有助于解释由自身抗体介导的自身免疫性视网膜病变的复杂临床症状，并可能有助于指导治疗策略。
