Machida S, Kondo M, Jamison J A, Khan N W, Kononen L T, Sugawara T, Bush R A, Sieving P A
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor 48105, USA.
Invest Ophthalmol Vis Sci. 2000 Sep;41(10):3200-9.
To correlate retinal functional changes with structural changes in P23H rhodopsin transgenic rats as a model of autosomal dominant retinitis pigmentosa.
P23H heterozygote (lines 1 and 3) and Sprague-Dawley control rats were studied at 4 to 29 weeks by retinal histology, electroretinogram (ERG), and a-wave transduction modeling.
Both line 1 (faster degeneration) and line 3 (slower degeneration) showed progressive rod outer segment (ROS) shortening and outer nuclear layer (ONL) cell loss with age. ERG b-wave maximum amplitude (Vb(max)) decreased with age, but b-wave threshold remained constant within each line despite progressive ONL thinning and ROS shortening. The only exception was in line 1 at 29 weeks, which showed a slight threshold change relative to earlier ages. Va(max) and a-wave threshold changed more rapidly and were more sensitive than the b-wave in reflecting histologic degeneration. Va(max) was linearly proportional to the product of (ROS x ONL) across a two log unit range of data combined from both lines. The photopic b-wave was normal for both lines until the ONL thinned beyond 50%. Phototransduction sensitivity was normal for both lines, and dark-adaptation recovery after bleaching rhodopsin was normal.
The P23H transgenic rat has a slow rod degeneration with initially normal cone function, consistent with clinical findings of P23H patients. However, the normal bleach recovery and the normal phototransduction sensitivity in this rat model are different from human P23H disease. a-Wave measures were more sensitive than the b-wave for tracking changes. b-Wave threshold was inexplicably poor for tracking degeneration. Although line 1 degenerated faster than line 3, the functional-structural correlates were the same. The tight linear relationship between saturated a-wave amplitude and the product of (ROS x ONL) indicates that the density of cGMP-gated channels per unit ROS plasma membrane area remains constant over a wide range of degenerations.
以常染色体显性遗传性视网膜色素变性模型P23H视紫红质转基因大鼠为研究对象，将视网膜功能变化与结构变化进行关联分析。
采用视网膜组织学、视网膜电图（ERG）及a波转导模型，对4至29周龄的P23H杂合子（1系和3系）大鼠及Sprague-Dawley对照大鼠进行研究。
1系（退变较快）和3系（退变较慢）均随年龄增长出现进行性视杆细胞外节（ROS）缩短和外核层（ONL）细胞丢失。ERG的b波最大振幅（Vb(max)）随年龄下降，但尽管ONL逐渐变薄和ROS缩短，每条品系内的b波阈值仍保持恒定。唯一的例外是29周龄的1系，其相对于早期年龄出现了轻微的阈值变化。Va(max)和a波阈值变化更快，在反映组织学退变方面比b波更敏感。在两条品系合并的两个对数单位的数据范围内，Va(max)与（ROS×ONL）的乘积呈线性比例关系。两条品系的明视b波在ONL变薄超过50%之前均正常。两条品系的光转导敏感性均正常，视紫红质漂白后的暗适应恢复也正常。
P23H转基因大鼠视杆细胞退变缓慢，最初视锥细胞功能正常，这与P23H患者的临床发现一致。然而，该大鼠模型中正常的漂白恢复和正常的光转导敏感性与人类P23H疾病不同。a波测量在追踪变化方面比b波更敏感。b波阈值在追踪退变方面表现异常差。尽管1系比3系退变更快，但功能-结构相关性相同。饱和a波振幅与（ROS×ONL）乘积之间紧密的线性关系表明，在广泛的退变范围内，单位ROS质膜面积上cGMP门控通道的密度保持恒定。
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