TULP1 Mutations Causing Early-Onset Retinal Degeneration: Preserved but Insensitive Macular Cones
TULP1 Mutations Causing Early-Onset Retinal Degeneration: Preserved but Insensitive Macular Cones
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DOI：
10.1167/iovs.14-14570
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发表时间：
2014-08-01
影响因子：
4.4
通讯作者：
Stone, Edwin M.
中科院分区：
文献类型：
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作者：
Jacobson, Samuel G.;Cideciyan, Artur V.;Stone, Edwin M.
目的.目的研究TULP 1（tubby-like protein 1）突变引起的视网膜变性（retinal degeneration，RD）患者的视功能和视网膜内外结构。通过动态和彩色静态视野检查、面部自体荧光成像和光谱域光学相干断层扫描（OCT）扫描研究了具有TULP 1突变的视网膜变性患者（n = 5;年龄范围，5-36岁）。测量视网膜外层和内层厚度，并绘制中央视网膜。与来自与四种纤毛病基因型（MAK、RPGR、BBS 1和USH 2A）相关的RD患者的结果进行比较。TULP 1-RD患者在生命的第一个十年就已经受到严重影响，并且存在快速进行性视力丧失。在任何年龄均无棒功能的证据。小的中央岛通过自体荧光成像显示黑化的视网膜色素上皮，并且通过OCT成像显示保存良好的感光层厚度。中心外的层状结构丢失，视网膜内层增厚。在TULP 1-RD患者和其他被认为是睫状体病的视网膜病中，进行了残余中央凹锥体岛的结构-功能关系。与其他患者不同，TULP 1-RD患者的黄斑中心凹结构紊乱程度更严重。伴有TULP 1突变的视网膜变性导致早期残留中心凹锥体的小中央岛。这些视锥细胞的敏感性低于残留结构的预期。人类表型与Tulp 1基因敲除小鼠模型中的实验证据一致，即视锥细胞外节近端的异常过程可能使视觉功能障碍复杂化。
PURPOSE. To investigate visual function and outer and inner retinal structure in the rare form of retinal degeneration (RD) caused by TULP1 (tubby-like protein 1) mutations.METHODS. Retinal degeneration patients with TULP1 mutations (n = 5; age range, 5-36 years) were studied by kinetic and chromatic static perimetry, en face autofluorescence imaging, and spectral-domain optical coherence tomography (OCT) scans. Outer and inner retinal laminar thickness were measured and mapped across the central retina. Comparisons were made with results from patients with RD associated with four ciliopathy genotypes (MAK, RPGR, BBS1, and USH2A).RESULTS. The TULP1-RD patients were severely affected already in the first decade of life and there was rapidly progressive visual loss. No evidence of rod function was present at any age. Small central islands showed melanized retinal pigment epithelium by autofluorescence imaging and well-preserved photoreceptor laminar thickness by OCT imaging. There was extracentral loss of laminar architecture and increased inner retinal thickening. Structure-function relationships in residual foveal cone islands were made in TULP1-RD patients and in other retinopathies considered ciliopathies. Patients with TULP1-RD, unlike the others, had greater dysfunction for the degree of foveal structural preservation.CONCLUSIONS. Retinal degeneration with TULP1 mutations leads to a small central island of residual foveal cones at early ages. These cones are less sensitive than expected from the residual structure. The human phenotype is consistent with experimental evidence in the Tulp1 knockout mouse model that visual dysfunction could be complicated by abnormal processes proximal to cone outer segments.