The Effect of Cone Opsin Mutations on Retinal Structure and the Integrity of the Photoreceptor Mosaic
The Effect of Cone Opsin Mutations on Retinal Structure and the Integrity of the Photoreceptor Mosaic
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DOI：
10.1167/iovs.12-11087
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发表时间：
2012-12-01
影响因子：
4.4
通讯作者：
Michaelides, Michel
中科院分区：
文献类型：
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作者：
Carroll, Joseph;Dubra, Alfredo;Michaelides, Michel
目的.评估OPN 1 LW和OPN 1 MW突变受试者的视网膜结构和光感受器镶嵌完整性。招募了11名受试者，其中8名先前已描述。使用从自适应光学扫描光检眼镜（AOSLO）获得的感光体马赛克的图像来测量视锥和视杆密度。使用横截面光谱域光学相干断层扫描（SD-OCT）图像测量总视网膜厚度、视网膜内层厚度和外核层+Henle纤维层（ONL+HFL）厚度。进行分子遗传学分析以表征OPN 1 LW/OPN 1 MW基因阵列。虽然在所有受试者中观察到视网膜分层和视锥镶嵌结构的破坏，但也观察到基因型特异性差异。例如，具有由祖先OPN 1 LW和OPN 1 MW基因混合引起的“L/M互换”突变的受试者在旁视皮层中具有显著的残留视锥结构（与正常的25%相似），尽管广泛的视网膜破坏包括大的中央凹病变和旁视皮层内视网膜变薄。这些受试者还报告了迟发型、进行性视觉功能丧失。相反，C203 R错义突变的受试者表现为先天性蓝锥单色性，视网膜分层缺陷仅限于ONL+HFL，残留锥结构的程度（正常的8%）与S-锥亚镶嵌的预期一致。与OPN 1 LW和OPN 1 MW突变相关的光感受器表型是高度可变的。这些发现对视蛋白突变受试者视觉功能的潜在恢复具有意义。我们的研究强调了高分辨率表型分析在遗传性视网膜疾病中表征细胞结构的重要性;这些信息对于选择最有可能对治疗干预做出反应的患者以及建立评估治疗疗效的基线至关重要。（Invest Ophthalmol维斯科学。2012;53：8006-8015）DOI：10.1167/iovs.12-11087
PURPOSE. To evaluate retinal structure and photoreceptor mosaic integrity in subjects with OPN1LW and OPN1MW mutations.METHODS. Eleven subjects were recruited, eight of whom have been previously described. Cone and rod density was measured using images of the photoreceptor mosaic obtained from an adaptive optics scanning light ophthalmoscope (AOSLO). Total retinal thickness, inner retinal thickness, and outer nuclear layer plus Henle fiber layer (ONL+HFL) thickness were measured using cross-sectional spectral-domain optical coherence tomography (SD-OCT) images. Molecular genetic analyses were performed to characterize the OPN1LW/OPN1MW gene array.RESULTS. While disruptions in retinal lamination and cone mosaic structure were observed in all subjects, genotype-specific differences were also observed. For example, subjects with "L/M interchange" mutations resulting from intermixing of ancestral OPN1LW and OPN1MW genes had significant residual cone structure in the parafovea (similar to 25% of normal), despite widespread retinal disruption that included a large foveal lesion and thinning of the parafoveal inner retina. These subjects also reported a later-onset, progressive loss of visual function. In contrast, subjects with the C203R missense mutation presented with congenital blue cone monochromacy, with retinal lamination defects being restricted to the ONL+HFL and the degree of residual cone structure (8% of normal) being consistent with that expected for the S-cone submosaic.CONCLUSIONS. The photoreceptor phenotype associated with OPN1LW and OPN1MW mutations is highly variable. These findings have implications for the potential restoration of visual function in subjects with opsin mutations. Our study highlights the importance of high-resolution phenotyping to characterize cellular structure in inherited retinal disease; such information will be critical for selecting patients most likely to respond to therapeutic intervention and for establishing a baseline for evaluating treatment efficacy. (Invest Ophthalmol Vis Sci. 2012;53:8006-8015) DOI: 10.1167/iovs.12-11087