Cone photoreceptor dysfunction in retinitis pigmentosa revealed by optoretinography.
Cone photoreceptor dysfunction in retinitis pigmentosa revealed by optoretinography.
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DOI：
10.1073/pnas.2107444118
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发表时间：
2021-11-23
影响因子：
11.1
通讯作者：
Miller DT
中科院分区：
文献类型：
--
作者：
Lassoued A;Zhang F;Kurokawa K;Liu Y;Bernucci MT;Crowell JA;Miller DT
许多致盲疾病都会影响光感受器，即视网膜中捕获和转换光以启动视觉的特殊细胞。对光感受器健康敏感的生物标志物对于这些疾病的早期检测和有效治疗监测至关重要，但仍然难以捉摸。在这里，我们开发了一种光学生物标志物，基于视视网膜照相感光器对光刺激的反应，该标志物反映了色素性视网膜炎（RP）患者个体视锥细胞感光器功能障碍的程度，RP是最常见的遗传性视网膜退行性疾病。我们的结果表明，这种生物标志物可能有助于评估 RP 患者剩余视网膜细胞的功能，以及评估基因治疗和干细胞移植等治疗方法对 RP 和其他影响光感受器疾病的疗效。色素性视网膜炎（RP）是最常见的遗传性视网膜退行性疾病，其最严重的阶段是视锥细胞死亡。视野测量和视网膜电图方法是诊断和监测 RP 以及评估视锥细胞功能的黄金标准。然而，这些方法缺乏空间分辨率和灵敏度来评估单个感光细胞水平上的疾病进展，而单个感光细胞是疾病的起源，其退化会导致视力丧失。高分辨率视网膜成像方法允许在体内观察人类视锥细胞，但直到最近才达到足够的灵敏度来观察视锥视网膜图中所显示的其功能。通过相敏自适应光学相干断层扫描成像，我们在视锥细胞视视网膜图中识别出一种生物标志物，该生物标志物通过用闪光刺激视锥细胞并测量其外节的纳米级变化来表征个体视锥细胞功能障碍。我们发现视锥细胞视视网膜造影反应随着 RP 严重程度的增加而降低，即使在视锥细胞密度看起来正常的区域，视锥细胞的反应也可能与对照组不同。出乎意料的是，在检查的最严重患病斑块中，我们发现孤立的锥体反应正常。研究发现，短波长敏感视锥细胞比中波长和长波长敏感视锥细胞更容易受到 RP 的影响。我们发现，在 RP 中，视锥细胞响应和视锥外节长度的减少早于视锥细胞密度的变化，但在单个视锥细胞内，响应和长度的减少不一定相关。
Many blinding diseases afflict photoreceptors, specialized cells in the retina that capture and transduce light to initiate vision. Biomarkers that are sensitive to photoreceptor health are crucial for early detection and effective treatment monitoring of these diseases yet remain elusive. Here, we develop an optical biomarker, based on optoretinographic photoreceptor responses to light stimulation, that reflects the degree of dysfunction of individual cone photoreceptors in patients with retinitis pigmentosa (RP), the most common inherited retinal degenerative disease. Our results show that this biomarker may be beneficial for assessing the functionality of remaining retinal cells in RP patients and for assessing efficacy of treatments such as gene therapy and stem cell transplantation for RP and other diseases afflicting photoreceptors. Retinitis pigmentosa (RP) is the most common group of inherited retinal degenerative diseases, whose most debilitating phase is cone photoreceptor death. Perimetric and electroretinographic methods are the gold standards for diagnosing and monitoring RP and assessing cone function. However, these methods lack the spatial resolution and sensitivity to assess disease progression at the level of individual photoreceptor cells, where the disease originates and whose degradation causes vision loss. High-resolution retinal imaging methods permit visualization of human cone cells in vivo but have only recently achieved sufficient sensitivity to observe their function as manifested in the cone optoretinogram. By imaging with phase-sensitive adaptive optics optical coherence tomography, we identify a biomarker in the cone optoretinogram that characterizes individual cone dysfunction by stimulating cone cells with flashes of light and measuring nanometer-scale changes in their outer segments. We find that cone optoretinographic responses decrease with increasing RP severity and that even in areas where cone density appears normal, cones can respond differently than those in controls. Unexpectedly, in the most severely diseased patches examined, we find isolated cones that respond normally. Short-wavelength–sensitive cones are found to be more vulnerable to RP than medium- and long-wavelength–sensitive cones. We find that decreases in cone response and cone outer-segment length arise earlier in RP than changes in cone density but that decreases in response and length are not necessarily correlated within single cones.
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X连锁性视网膜炎的患者外部段层进展的光谱域光学相干断层扫描测量。
影响因子：
8.1
作者：
Birch, David G.;Locke, Kirsten G.;Wen, Yuquan;Locke, Kelly I.;Hoffman, Dennis R.;Hood, Donald C.
通讯作者：
Hood, Donald C.
DOI：
10.1073/pnas.1606428113
发表时间：
2016-11-15
影响因子：
11.1
作者：
Hillmann, Dierck;Spahr, Hendrik;Huettmann, Gereon
通讯作者：
Huettmann, Gereon
DOI：
10.1007/978-3-319-17121-0_39
发表时间：
2016-01-01
期刊：
RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY
影响因子：
--
作者：
Gale, Michael J.;Feng, Shu;Pennesi, Mark E.
通讯作者：
Pennesi, Mark E.
影响因子：
4.4
作者：
Duncan, Jacque L.;Zhang, Yuhua;Roorda, Austin
通讯作者：
Roorda, Austin
DOI：
10.1056/nejmoa1412965
发表时间：
2015-05-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Jacobson SG;Cideciyan AV;Roman AJ;Sumaroka A;Schwartz SB;Heon E;Hauswirth WW
通讯作者：
Hauswirth WW