Complement-independent retinal pathology produced by intravitreal injection of neuromyelitis optica immunoglobulin G.
Complement-independent retinal pathology produced by intravitreal injection of neuromyelitis optica immunoglobulin G.
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DOI：
10.1186/s12974-016-0746-9
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发表时间：
2016-10-20
影响因子：
9.3
通讯作者：
Verkman AS
中科院分区：
文献类型：
--
作者：
Felix CM;Levin MH;Verkman AS
视神经脊髓炎 (NMO) 是一种中枢神经系统自身免疫性炎症性疾病，通常与视网膜异常相关，包括视网膜神经纤维层变薄和微囊性改变。在这里，我们证明抗水通道蛋白 4 自身抗体 (AQP4-IgG) 的被动转移会产生原发性视网膜病理。通过玻璃体内注射将 AQP4-IgG 递送至成年大鼠视网膜。通过免疫荧光评估大鼠视网膜和视网膜外植体培养物。免疫荧光显示 AQP4-IgG 沉积在视网膜 Müller 细胞上，5 天后 AQP4 表达大大降低，胶质纤维酸性蛋白增加。 30 天时，出现轻度视网膜炎症，伴有小胶质细胞活化，但白细胞浸润很少，视网膜神经节细胞损失，神经节细胞复合体变薄。有趣的是，AQP4 的丧失与补体无关，如在眼镜蛇毒因子治疗的大鼠和给予缺乏补体效应功能的突变 AQP4-IgG 的正常大鼠中所见。将离体视网膜培养物暴露于 AQP4-IgG 中，24 小时内 AQP4 表达显着降低，这在很大程度上被内吞作用或溶酶体酸化抑制剂所阻止。 AQP4-IgG 的被动转移导致原发性、补体独立的视网膜病理学，这可能导致 NMO 患者出现视网膜异常。
Neuromyelitis optica (NMO), an autoimmune inflammatory disease of the central nervous system, is often associated with retinal abnormalities including thinning of the retinal nerve fiber layer and microcystic changes. Here, we demonstrate that passive transfer of an anti-aquaporin-4 autoantibody (AQP4-IgG) produces primary retinal pathology. AQP4-IgG was delivered to adult rat retinas by intravitreal injection. Rat retinas and retinal explant cultures were assessed by immunofluorescence. Immunofluorescence showed AQP4-IgG deposition on retinal Müller cells, with greatly reduced AQP4 expression and increased glial fibrillary acidic protein by 5 days. There was mild retinal inflammation with microglial activation but little leukocyte infiltration and loss of retinal ganglion cells by 30 days with thinning of the ganglion cell complex. Interestingly, the loss of AQP4 was complement independent as seen in cobra venom factor-treated rats and in normal rats administered a mutated AQP4-IgG lacking complement effector function. Exposure of ex vivo retinal cultures to AQP4-IgG produced a marked reduction in AQP4 expression by 24 h, which was largely prevented by inhibitors of endocytosis or lysosomal acidification. Passive transfer of AQP4-IgG results in primary, complement-independent retinal pathology, which might contribute to retinal abnormalities seen in NMO patients.
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影响因子：
11.2
作者：
Bennett, Jeffrey L.;Lam, Chiwah;Kalluri, Sudhakar Reddy;Saikali, Philippe;Bautista, Katherine;Dupree, Cecily;Glogowska, Magdalena;Case, David;Antel, Jack P.;Owens, Gregory P.;Gilden, Don;Nessler, Stefan;Stadelmann, Christine;Hemmer, Bernhard
通讯作者：
Hemmer, Bernhard
DOI：
10.1016/s1474-4422(12)70133-3
发表时间：
2012-06
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Papadopoulos MC;Verkman AS
通讯作者：
Verkman AS
DOI：
10.1177/1352458514567216
发表时间：
2015-05
期刊：
Multiple sclerosis (Houndmills, Basingstoke, England)
影响因子：
--
作者：
Bennett JL;de Seze J;Lana-Peixoto M;Palace J;Waldman A;Schippling S;Tenembaum S;Banwell B;Greenberg B;Levy M;Fujihara K;Chan KH;Kim HJ;Asgari N;Sato DK;Saiz A;Wuerfel J;Zimmermann H;Green A;Villoslada P;Paul F;GJCF-ICC&BR
通讯作者：
GJCF-ICC&BR
影响因子：
12.7
作者：
Misu T;Höftberger R;Fujihara K;Wimmer I;Takai Y;Nishiyama S;Nakashima I;Konno H;Bradl M;Garzuly F;Itoyama Y;Aoki M;Lassmann H
通讯作者：
Lassmann H
影响因子：
5.3
作者：
Geis, Christian;Ritter, Christian;Ruschil, Christoph;Weishaupt, Andreas;Gruenewald, Benedikt;Stoll, Guido;Holmoy, Trygve;Misu, Tatsuro;Fujihara, Kazuo;Hemmer, Bernhard;Stadelmann, Christine;Bennett, Jeffrey L.;Sommer, Claudia;Toyka, Klaus V.
通讯作者：
Toyka, Klaus V.