Rod and Cone Mediated Function in Retinal Disease

视杆细胞和视锥细胞在视网膜疾病中介导的功能

• 批准号: 10246743
• 负责人: Brett Jeffrey
• 金额: $ 43.87万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10246743
• 关键词: Affect; Australia; Cessation of life; Cladribine; Clinical; Clinical Trials; Color; Cone; Custom; Dark Adaptation; Discrimination; Disease; Disease Progression; Early Diagnosis; FDA approved; Family; Family member; Frequencies; Functional disorder; Kinetics; Light; Measures; Mediating; Methods; Modification; Monitor; Normal Range; Outcome Measure; Participant; Patients; Pattern; Perimetry; Psychophysics; Radial; Retina; Retinal Cone; Retinal Degeneration; Retinal Diseases; Rod; Shapes; Stimulus; Structure; Symptoms; Testing; Time; Variant; Vertebrate Photoreceptors; Visual Fields; aged; healthy volunteer; interest; late-onset retinal degeneration; macula; member; phenotypic biomarker; retinal rods

Specific Aim 1: To establish the normal ranges of dark-adapted retinal sensitivities for the Medmont, and for RF hyperacuity function on the Display++ monitor in healthy volunteers. Dark-adapted retinal sensitivity has been measured with the Medmont from 44 healthy volunteers aged between 16 and 67 years. To be examine rod photoreceptor function, we developed a scotopic version of radial frequency (RF) hyperacuity test using the Display++. Such a scotopic shape discrimination task has not previously been described. We have measured scotopic shape discrimination from 39 healthy volunteers aged between16 and 80 years (some participants also completed retinal sensitivity and dark adaptation testing). Specific Aim 2: To establish the normal ranges for the kinetics of dark adaptation for the Medmont DAC blue and red stimuli in healthy volunteers. Dark adaptation has been measured with the Medmont from 32 healthy volunteers aged between 16 and 53 years (participants were the same recorded for retinal sensitivity). Specific Aim 3: To quantify local changes in rod and cone photoreceptor function across the retina in participants with retinal disease. Delayed dark adaptation (DA) is an early phenotypic marker in late onset retinal degeneration (L-ORD) and may precede symptoms and retinal changes. We used the Medmont to measure rod-mediated function in seven members of a family with L-ORD. Rod function was most severely affected in the temporal retina where structural changes are first observed in this disease. Notably, the spatial variation in loss of rod-mediated function varies between family members and local loss of rod function across the retina precedes structural change. We have followed two patients of one family over a period of three years to document disease progression. We have also documented for the first time in L-ORD patients the existence of a rod-plateau following different levels of rod-bleaching. We have shown spatial variation in rod function in AMD patients with and without reticular pseudodrusen (RPD) using both the Medmont and radial frequency hyperacuity test. AMD patients with RPD are on particular interest because of their dramatically delayed dark adaptation which is also observed in patients with L-ORD and Sorsbys .

具体目标1：在健康志愿者中建立Medmont暗适应视网膜灵敏度的正常范围，以及Display++监视器上RF超敏功能的正常范围。 用Medmont测量了44名年龄在16至67岁之间的健康志愿者的暗适应视网膜敏感度。 为了检查视杆细胞的功能，我们使用Display++开发了一种暗视版本的径向频率（RF）超敏度测试。 这样的暗视形状辨别任务先前未被描述。 我们测量了39名年龄在16岁至80岁之间的健康志愿者的暗视形状辨别力（一些参与者还完成了视网膜敏感度和暗适应测试）。 具体目标2：确定健康志愿者中Medmont DAC蓝色和红色刺激的暗适应动力学的正常范围。 使用Medmont测量了32名年龄在16至53岁之间的健康志愿者的暗适应（参与者的视网膜敏感性记录相同）。 具体目标3：量化视网膜疾病受试者视网膜上视杆细胞和视锥细胞感光功能的局部变化。 延迟暗适应（DA）是晚发性视网膜变性（L-ORD）的早期表型标志物，可能先于症状和视网膜变化。我们使用Medmont测量了一个L-ORD家族的7名成员的视杆介导的功能。视杆功能在颞叶视网膜中受到最严重的影响，在这种疾病中首次观察到结构变化。 值得注意的是，视杆介导的功能丧失的空间变化在家族成员之间变化，并且视网膜上视杆功能的局部丧失先于结构变化。 我们对一个家庭的两名患者进行了为期三年的随访，以记录疾病进展。 我们还首次在L-ORD患者中记录了不同程度的棒漂白后棒平台的存在。 我们使用Medmont和径向频率超敏度测试显示了伴有和不伴有网状假性玻璃疣（RPD）的AMD患者视杆功能的空间变化。患有RPD的AMD患者特别感兴趣，因为他们的暗适应显著延迟，这在L-ORD和Sorsbys患者中也观察到。