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: 9555713
• 负责人: Brett Jeffrey
• 金额: $ 7.88万
• 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/9555713
• 关键词: Age; Australia; Cessation of life; Cladribine; Clinical; Clinical Trials; Color; Cone; Custom; Dark Adaptation; Darkness; Disease; Early Diagnosis; Exposure to; FDA approved; Functional disorder; Fundus; Hereditary Disease; Hour; Kinetics; Light; Location; Measures; Mediating; Methods; Modification; Normal Range; Outcome Measure; Participant; Patients; Pattern; Perimetry; Phenotype; Pigmentary retinal dystrophy; Protocols documentation; Psychophysics; Reporting; Retina; Retinal; Retinal Cone; Retinal Degeneration; Retinal Diseases; Rhodopsin; Severities; Source; Stimulus; Time; Tungsten; Vertebrate Photoreceptors; Visual Fields; base; healthy volunteer; instrument; macula; retinal rods; trend

The first two Aims of this protocol require establishing the normal ranges for dark-adapted retinal sensitivity and the kinetics of dark adaptation using a new instrument, the Medmont dark-adapted chromatic (DAC) perimeter. Specific Aim 1: To establish the normal ranges of dark-adapted retinal sensitivities for the Medmont red and blue stimuli in healthy volunteers. With 2-color dark-adapted perimetry, calculation of the difference in dark-adapted retinal sensitivity to blue and red stimuli is fundamental to determining whether a sensitivity at a given retinal location is mediated by rods and/or cones. We have established preliminary normal values for mean ( SD) dark-adapted retinal sensitivities for the blue (57.9 1.9 dB) and red (35.5 1.6 dB) stimuli, and for the difference in sensitivity between these two colors (22.5 1.7 dB). The mean difference obtained with the Medmont DAC is close to previously reported difference values of 18 dB and 19 dB for LCD and tungsten sources respectively. The direct implication of our result is that a difference value of less than 19.1 dB (mean 2SD) would indicate abnormal rod function in a patient. Dark-adapted retinal sensitivity was not significantly correlated with age although there was a trend for lower blue sensitivity with age. 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. The time course of dark adaptation has historically been measured clinically following exposure to an achromatic background light that bleaches approximately 50-100% of rhodopsin. Given that dark adaptation can be very delayed (several hours) in patients with AMD and some genetic disorders (e.g. Fundus Albipunctatus) and many patients with retinal degenerations have marked photo aversion, we are seeking to examine the kinetics of dark adaptation to smaller bleaches. We examined the kinetics of dark adaptation to a range of bleaches (30-60%) obtained by varying background light exposures (duration, intensity, color). To date, a 30% rhodopsin bleach obtained by a 5-minute exposure to 505 nm light has been tolerated by all participants and this will be our default for AMD subjects (see below). Specific Aim 3: To quantify local changes in rod and cone photoreceptor function across the retina in participants with retinal disease. We examined dark adapted thresholds and dark-adaptation kinetics in AMD participants who were categorized into five AMD severity groups based on fundus features. Elevation in DA thresholds across the central retina worsened with increasing AMD severity. RIT increased with AMD group and eccentricity (P<0.001 for both). RITslope, defined as the change in RIT with retinal eccentricity, increased with AMD severity (P<0.0001). Three dark-adaptation phenotypes emerged: normal dark-adapted function (DA1), normal thresholds but slowed DA (DA2), and elevated DA thresholds with slowed DA kinetics (DA3). Aberrant dark adaptation occurred at 32% of loci with no local structural changes and 100% of loci with SDD or ellipsoid band disruption.

该协议的前两个目标需要使用新仪器 Medmont 暗适应色度 (DAC) 周长建立暗适应视网膜敏感性和暗适应动力学的正常范围。 具体目标 1：建立健康志愿者暗适应视网膜对梅德蒙特红和蓝刺激的敏感度的正常范围。 通过 2 色暗适应视野检查，计算暗适应视网膜对蓝色和红色刺激的敏感性差异对于确定给定视网膜位置的敏感性是否由视杆细胞和/或视锥细胞介导至关重要。 我们已经建立了蓝色（57.9±1.9dB）和红色（35.5±1.6dB）刺激的平均（SD）暗适应视网膜敏感性的初步正常值，以及这两种颜色之间的敏感性差异（22.5±1.7dB）。 使用 Medmont DAC 获得的平均差异接近于之前报告的 LCD 光源和钨丝光源分别为 18 dB 和 19 dB 的差异值。 我们的结果的直接含义是，小于 19.1 dB（平均 2SD）的差异值将表明患者的杆功能异常。 尽管随着年龄的增长，蓝色敏感性有降低的趋势，但暗适应视网膜敏感性与年龄没有显着相关。 具体目标 2：建立健康志愿者中 Medmont DAC 蓝色和红色刺激的暗适应动力学的正常范围。 历史上，暗适应的时间进程在临床上是在暴露于消色差背景光后测量的，该背景光漂白了大约 50-100% 的视紫红质。 鉴于AMD和某些遗传性疾病（例如眼底白斑）患者的暗适应可能会非常延迟（几个小时），并且许多视网膜变性患者有明显的厌光现象，我们正在寻求研究对较小漂白剂的暗适应动力学。 我们研究了通过改变背景光暴露（持续时间、强度、颜色）获得的一系列漂白剂（30-60%）的暗适应动力学。 迄今为止，所有参与者都可以耐受通过 505 nm 光照射 5 分钟获得的 30% 视紫红质漂白剂，这将是我们对 AMD 受试者的默认设置（见下文）。 具体目标 3：量化患有视网膜疾病的参与者视网膜上视杆细胞和视锥细胞光感受器功能的局部变化。 我们检查了 AMD 参与者的暗适应阈值和暗适应动力学，根据眼底特征将这些参与者分为五个 AMD 严重程度组。 随着 AMD 严重程度的增加，中央视网膜 DA 阈值的升高程度也随之恶化。 RIT随着AMD组和偏心率的增加而增加（两者P<0.001）。 RITslope 定义为 RIT 随视网膜偏心率的变化，随着 AMD 严重程度的增加而增加 (P<0.0001)。出现了三种暗适应表型：正常的暗适应功能 (DA1)、正常阈值但 DA 减慢 (DA2) 以及 DA 阈值升高但 DA 动力学减慢 (DA3)。 32% 的基因座发生异常暗适应，没有局部结构变化，100% 的基因座发生 SDD 或椭球带破坏。