Section of Immunopathology, Laboratory of Immunology, National Eye Institute, National Institutes of Health, NIH/NEI, Bethesda, MD 20892-1857, USA.
BMC Ophthalmol. 2012 Nov 13;12:56. doi: 10.1186/1471-2415-12-56.
Paraneoplastic retinopathy is caused by the cross-reaction of neoplasm-directed autoantibodies against retinal antigens and results in retinal damage. Paraneoplastic vitelliform retinopathy, a presumed paraneoplastic retinopathy with features of atypical melanoma-associated retinopathy, has recently been reported in patients with metastatic melanoma. Ocular ultrastructure and its autoantibody localization of paraneoplastic vitelliform retinopathy are still indefinable. This is the first report of anti-transient receptor potential M1 antibody directly against human retinal bipolar dendritic tips in a melanoma patient with paraneoplastic vitelliform retinopathy.
We present a pair of postmortem eyes of an 80-year-old male with metastatic cutaneous melanoma, who developed paraneoplastic vitelliform retinopathy. The autopsied eyes were examined with light microscopy, immunohistochemistry, and transmission electron microscopy. Microscopically, the inner nuclear layer and outer plexiform layer were the most affected retinal structures, with local thinning. The lesions extended to the outer nuclear layer, resulting in focal retinal degeneration, edema, and atrophy. No active inflammation or melanoma cells were observed. Immunohistochemistry showed tightly compact bipolar cell nuclei (protein kinase C alpha/calbindin positive) with blur/loss of ON bipolar cell dendritic tips (transient receptor potential M1 positive) in diffusely condensed outer plexiform layer. The metastatic melanoma cells in his lung also showed immunoreactivity against transient receptor potential M1 antibody. Transmission electron microscopy illustrated degenerated inner nuclear layer with disintegration of cells and loss of cytoplasmic organelles. These cells contained many lysosomal and autophagous bodies and damaged mitochondria. Their nuclei appeared pyknotic and fragmentary. The synapses in the outer plexiform layer were extensively degenerated and replaced with empty vacuoles and disintegrated organelles.
This case provides a convincing histological evidence of melanoma-associated autoantibodies directly against transient receptor potential M1 channels that target the ON bipolar cell structures in the inner nuclear and outer plexiform layers in paraneoplastic vitelliform retinopathy.
副肿瘤性视网膜病变是由针对视网膜抗原的肿瘤定向自身抗体的交叉反应引起的，导致视网膜损伤。副肿瘤性类 vitelliform 视网膜病变，一种具有非典型性黑色素瘤相关视网膜病变特征的假定副肿瘤性视网膜病变，最近在转移性黑色素瘤患者中报道。副肿瘤性类 vitelliform 视网膜病变的眼部超微结构及其自身抗体定位仍不明确。这是首例报道抗瞬时受体电位 M1 抗体直接针对黑色素瘤患者伴副肿瘤性类 vitelliform 视网膜病变的人视网膜双极树突末梢。
我们介绍了一对 80 岁男性的尸检眼球，该患者患有转移性皮肤黑色素瘤，并发副肿瘤性类 vitelliform 视网膜病变。对尸检眼球进行了光镜、免疫组织化学和透射电镜检查。显微镜下，内层核和外丛状层是受影响最严重的视网膜结构，出现局部变薄。病变延伸至外核层，导致局灶性视网膜变性、水肿和萎缩。未见活动性炎症或黑色素瘤细胞。免疫组化显示紧密致密的双极细胞核（蛋白激酶 C alpha/钙结合蛋白阳性），弥漫性凝聚的外丛状层中 ON 双极细胞树突末梢模糊/缺失（瞬时受体电位 M1 阳性）。他肺部的转移性黑色素瘤细胞也对瞬时受体电位 M1 抗体表现出免疫反应性。透射电镜显示内层核退化，细胞解体，细胞质细胞器丢失。这些细胞含有许多溶酶体和自噬体以及受损的线粒体。它们的核呈固缩和片段化。外丛状层中的突触广泛退化，被空泡和解体的细胞器取代。
本病例提供了令人信服的组织学证据，证明黑色素瘤相关自身抗体直接针对瞬时受体电位 M1 通道，该通道在副肿瘤性类 vitelliform 视网膜病变的内层核和外丛状层中的 ON 双极细胞结构中靶向作用。
