Cone Structure in Retinal Degeneration Associated with Mutations in the peripherin/RDS Gene
Cone Structure in Retinal Degeneration Associated with Mutations in the peripherin/RDS Gene
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DOI：
10.1167/iovs.10-6549
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发表时间：
2011-03-01
影响因子：
4.4
通讯作者：
Roorda, Austin
中科院分区：
文献类型：
--
作者：
Duncan, Jacque L.;Talcott, Katherine E.;Roorda, Austin
目的.目的：研究视锥细胞结构和功能与外周蛋白/RDS第二环区突变的关系。采用自适应光学扫描激光检眼镜和光谱域光学相干断层扫描技术对4例外周蛋白/RDS突变患者和27例年龄相似的健康受试者进行高分辨率黄斑图像检查。视网膜结构和眼底自发荧光（AF）的测量与视功能相关，包括最佳矫正视力（BCVA）、动态和静态视野检查、眼底引导微视野检查、全视野视网膜电图（ERG）和多焦ERG。对每个患者外周蛋白/RDS基因的编码区进行测序。外周蛋白/RDS中的杂合突变预计会影响每位患者第二椎间盘内结构域的蛋白质结构（Arg 172 Trp、Gly 208 Asp、Pro210 Arg和Cys 213 Tyr）。每例患者研究眼的BCVA至少为20/32。患者1存在弥漫性视锥大于视杆功能障碍，而患者4存在视杆大于视锥功能障碍;所有患者均存在黄斑外视网膜功能障碍。黄斑AF是异质性的，除了患者1显示锥-杆营养不良外，所有患者的光感受器-视网膜色素上皮（RPE）连接层在中心凹处均显示反射率增加。锥填充不规则，每个患者在中央4度的大多数位置锥间距显著增加（z分数>2）。外周蛋白/RDS突变产生弥漫性AF异常，感光细胞/RPE连接的破坏，以及增加的视锥间距，与黄斑中的视锥丢失一致。观察到的异常表明，第二椎间盘内域的外周/RDS的完整性是至关重要的正常黄斑锥结构。（Invest Invest Ophthalmol维斯科学）2011;52：1557-1566）DOI：10.1167/iovs.10-6549
PURPOSE. To study cone photoreceptor structure and function associated with mutations in the second intradiscal loop region of peripherin/RDS.METHODS. High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in four patients with peripherin/RDS mutations and 27 age-similar healthy subjects. Measures of retinal structure and fundus autofluorescence (AF) were correlated with visual function, including best-corrected visual acuity (BCVA), kinetic and static perimetry, fundus-guided microperimetry, full-field electroretinography (ERG), and multifocal ERG. The coding regions of the peripherin/RDS gene were sequenced in each patient.RESULTS. Heterozygous mutations in peripherin/RDS were predicted to affect protein structure in the second intradiscal domain in each patient (Arg172Trp, Gly208Asp, Pro210Arg and Cys213Tyr). BCVA was at least 20/32 in the study eye of each patient. Diffuse cone-greater-than-rod dysfunction was present in patient 1, while rod-greater-than-cone dysfunction was present in patient 4; macular outer retinal dysfunction was present in all patients. Macular AF was heterogeneous, and the photoreceptor-retinal pigment epithelial (RPE) junction layer showed increased reflectivity at the fovea in all patients except patient 1, who showed cone-rod dystrophy. Cone packing was irregular, and cone spacing was significantly increased (z-scores >2) at most locations throughout the central 4 degrees in each patient.CONCLUSIONS. peripherin/RDS mutations produced diffuse AF abnormalities, disruption of the photoreceptor/RPE junction, and increased cone spacing, consistent with cone loss in the macula. The abnormalities observed suggest that the integrity of the second intradiscal domain of peripherin/RDS is critical for normal macular cone structure. (Invest Invest Ophthalmol Vis Sci. 2011;52:1557-1566) DOI:10.1167/iovs.10-6549