Luo Xunda, Cideciyan Artur V, Iannaccone Alessandro, Roman Alejandro J, Ditta Lauren C, Jennings Barbara J, Yatsenko Svetlana A, Sheplock Rebecca, Sumaroka Alexander, Swider Malgorzata, Schwartz Sharon B, Wissinger Bernd, Kohl Susanne, Jacobson Samuel G
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Hamilton Eye Institute, Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
PLoS One. 2015 Apr 24;10(4):e0125700. doi: 10.1371/journal.pone.0125700. eCollection 2015.
Blue Cone Monochromacy (BCM) is an X-linked retinopathy caused by mutations in the OPN1LW / OPN1MW gene cluster, encoding long (L)- and middle (M)-wavelength sensitive cone opsins. Recent evidence shows sufficient structural integrity of cone photoreceptors in BCM to warrant consideration of a gene therapy approach to the disease. In the present study, the vision in BCM is examined, specifically seeking clinically-feasible outcomes for a future clinical trial.
BCM patients (n = 25, ages 5-72) were studied with kinetic and static chromatic perimetry, full-field sensitivity testing, and eye movement recordings. Vision at the fovea and parafovea was probed with chromatic microperimetry.
Kinetic fields with a Goldmann size V target were generally full. Short-wavelength (S-) sensitive cone function was normal or near normal in most patients. Light-adapted perimetry results on conventional background lights were abnormally reduced; 600-nm stimuli were seen by rods whereas white stimuli were seen by both rods and S-cones. Under dark-adapted conditions, 500-nm stimuli were seen by rods in both BCM and normals. Spectral sensitivity functions in the superior retina showed retained rod and S-cone functions in BCM under dark-adapted and light-adapted conditions. In the fovea, normal subjects showed L/M-cone mediation using a 650-nm stimulus under dark-adapted conditions, whereas BCM patients had reduced sensitivity driven by rod vision. Full-field red stimuli on bright blue backgrounds were seen by L/M-cones in normal subjects whereas BCM patients had abnormally reduced and rod-mediated sensitivities. Fixation location could vary from fovea to parafovea. Chromatic microperimetry demonstrated a large loss of sensitivity to red stimuli presented on a cyan adapting background at the anatomical fovea and surrounding parafovea.
BCM rods continue to signal vision under conditions normally associated with daylight vision. Localized and retina-wide outcome measures were examined to evaluate possible improvement of L/M-cone-based vision in a clinical trial.
蓝锥单色素视（BCM）是一种X连锁视网膜病变，由编码长（L）和中（M）波长敏感视锥蛋白的OPN1LW / OPN1MW基因簇突变引起。最近的证据表明，BCM中视锥光感受器具有足够的结构完整性，值得考虑采用基因治疗方法来治疗该疾病。在本研究中，对BCM患者的视力进行了检查，特别寻找未来临床试验中临床可行的结果。
对25例BCM患者（年龄5 - 72岁）进行了动态和静态色觉视野检查、全视野敏感度测试以及眼动记录。用彩色微视野计探测中央凹和旁中央凹的视力。
使用戈德曼V型视标测得的动态视野通常完整。大多数患者的短波（S）敏感视锥功能正常或接近正常。在传统背景光下的明适应视野检查结果异常降低；600纳米刺激由视杆细胞感知，而白色刺激由视杆细胞和S视锥细胞共同感知。在暗适应条件下，BCM患者和正常受试者的视杆细胞均能感知500纳米刺激。在暗适应和明适应条件下，BCM患者视网膜上部的光谱敏感度函数显示视杆细胞和S视锥细胞功能保留。在中央凹，正常受试者在暗适应条件下使用650纳米刺激时显示L/M视锥细胞介导，而BCM患者由视杆细胞视觉驱动的敏感度降低。正常受试者在亮蓝色背景下的全视野红色刺激由L/M视锥细胞感知，而BCM患者的敏感度异常降低且由视杆细胞介导。注视位置可能从中央凹变化到旁中央凹。彩色微视野计显示，在解剖学中央凹和周围旁中央凹处，在青色适应背景下呈现的红色刺激的敏感度大幅下降。
在通常与明视觉相关的条件下，BCM视杆细胞继续传递视觉信号。检查了局部和全视网膜的结果指标，以评估在临床试验中基于L/M视锥细胞的视力可能得到的改善。
