Disease Boundaries in the Retina of Patients with Usher Syndrome Caused by MYO7A Gene Mutations
Disease Boundaries in the Retina of Patients with Usher Syndrome Caused by MYO7A Gene Mutations
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DOI：
10.1167/iovs.08-3122
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发表时间：
2009-04-01
影响因子：
4.4
通讯作者：
Kimberling, William J.
中科院分区：
文献类型：
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作者：
Jacobson, Samuel G.;Aleman, Tomas S.;Kimberling, William J.
目的。研究由 MYO7A 突变引起的 1B 型亚瑟综合症 (USH1B) 的视网膜微观结构，作为治疗举措的前奏。方法。通过光学相干断层扫描对 MYO7A-USH1B 患者（n = 17；年龄 5-61）进行了研究。测量了水平和垂直子午线的视网膜层。使用自动视野检查法测量共定位视觉敏感度，以比较过渡区的功能和结构。结果。 MYO7A-USH1B 中央视网膜的层状结构范围从正常到严重异常。在正常和异常视网膜之间的过渡区内，第一个可检测到的异常是 OLM（外界膜）的突出度增加。 ONL 厚度下降伴随着 OPL 厚度增加以及 INL 正常或增加。无法检测到的 ONL 和 OPL 以及超厚的 INL 是过渡区进一步偏心处严重椎板病变的特征。过渡区的视觉灵敏度随着 ONL 厚度的减小而下降。结论。 MYO7A-USH1B 患者的视网膜区域可能具有结构和功能正常的区域，但可明显转变为严重的椎板病变和视力丧失。最早可检测到的疾病结构标志物可能代表米勒神经胶质细胞对光感受器应激和细胞凋亡的反应。可以预见的是，视觉损失与 ONL 厚度的下降有关。 MYO7A-USH1B 的局部治疗（例如视网膜下基因治疗）的前景提示需要确定需要在早期试验中考虑进行治疗的视网膜位置。过渡区是治疗的候选部位，层状结构和视觉敏感性是评估安全性和有效性的可能结果。 （投资眼科可见科学。2009 年；50：1886-1894）DOI：10.1167/iovs.08-3122
PURPOSE. To study retinal microstructure in Usher Syndrome type 1B (USH1B) caused by MYO7A mutations as a prelude to treatment initiatives.METHODS. Patients with MYO7A-USH1B (n = 17; ages 5-61) were studied with optical coherence tomography. Retinal laminae across horizontal and vertical meridians were measured. Colocalized visual sensitivity was measured with automated perimetry to enable comparisons of function and structure in the transition zones.RESULTS. Laminar architecture of the central retina in MYO7A-USH1B ranged from normal to severely abnormal. Within the transition zone between normal and abnormal retina, the first detectable abnormality was an increase in prominence of the OLM (outer limiting membrane). Declining ONL thickness was accompanied by increased thickness of the OPL and normal or increased INL. Undetectable ONL and OPL and hyperthick INL were features of severe laminopathy at further eccentricities into the transition zone. Visual sensitivity in the transition zone declined with the decrease in ONL thickness.CONCLUSIONS. Patients with MYO7A-USH1B can have regions of structurally and functionally normal retina with definable transitions to severe laminopathy and visual loss. The earliest detectable structural markers of disease may represent Muller glial cell response to photoreceptor stress and apoptosis. Visual losses were predictably related to a decline in ONL thickness. The prospect of focal treatment of MYO7A-USH1B, such as subretinal gene therapy, prompts the need to identify retinal locations that warrant consideration for treatment in early phase trials. The transition zones are candidate sites for treatment, and laminar architecture and visual sensitivity are possible outcomes to assess safety and efficacy. (Invest Ophthalmol Vis Sci. 2009; 50: 1886-1894) DOI: 10.1167/iovs.08-3122