Martin Rex E, Ranchon-Cole Isabelle, Brush Richard S, Williamson Clint R, Hopkins Steven A, Li Feng, Anderson Robert E
Department of Cell Biology, University of Oklahoma Health Sciences Center, Dean A. McGee Eye Institute, Oklahoma City, OK 73104, USA.
Mol Vis. 2004 Mar 26;10:199-207.
The n-3 polyunsaturated fatty acids (PUFA) facilitate retinal development and function. Rats carrying transgenes with P23H and S334ter rhodopsin mutations lose their photoreceptors and have lower levels of 22:6n-3 in rod photoreceptor outer segments (ROS) than wild type (WT) animals. We tested the hypothesis that the rate of retinal degeneration in these mutant animals could be sensitive to the n-3 fatty acid content of retina.
Beginning embryonic day 15, WT and heterozygous transgenic rats with P23H and S344ter rhodopsin mutations were fed semi-synthetic diets enriched in n-6 (safflower oil, SO) or n-3 (flaxseed oil, FO) PUFA. At 35 and 55 days of age, electroretinographic (ERG) response, outer nuclear layer (ONL) thickness, and fatty acid composition of plasma and ROS were determined. Student's t-tests and multivariate analysis of variance with post hoc tests determined statistical differences.
Rats fed FO or SO diets had different n-6/n-3 PUFA ratios in plasma (1.3 and 62) and ROS (0.2 and 1.1, respectively). Although there were profound effects of the diets on the plasma fatty acid composition, there were only minor differences between WT and transgenic animals within each dietary regime. The ROS of FO fed rats had 70% more 22:6n-3 than those fed SO, and the WT had higher concentrations of 22:6n-3 than the transgenic animals (WT>P23H>S334ter). In contrast, there was no difference in 22:6n-3 levels in ROS of WT and transgenic rats fed the SO diet. At P55, both transgenic lines had diminished ERGs and ONL thickness relative to the WT. There was no detectable effect of ROS fatty acid enrichment on the rate of retinal degeneration in the transgenic animals. However, the FO-diet provided a modest protection of function (b-wave) in S334ter animals.
Feeding n-3 fatty acids to rats with mutant rhodopsin transgenes significantly increased the levels of 22:6n-3 in ROS membranes, but had no effect on the rate of retinal degeneration. Therefore, the degeneration is not the result of low (or high) 22:6n-3 in ROS and supplementation with 18:3n-3 will not rescue dying photoreceptor cells in these animal models of inherited retinal degenerations.
n-3多不饱和脂肪酸（PUFA）有助于视网膜发育和功能。携带P23H和S334ter视紫红质突变转基因的大鼠会失去其光感受器，并且其视杆光感受器外段（ROS）中的22:6n-3水平低于野生型（WT）动物。我们检验了这样一个假设，即这些突变动物的视网膜退化速率可能对视网膜的n-3脂肪酸含量敏感。
从胚胎第15天开始，给野生型以及携带P23H和S344ter视紫红质突变的杂合转基因大鼠喂食富含n-6（红花油，SO）或n-3（亚麻籽油，FO）PUFA的半合成饲料。在35日龄和55日龄时，测定视网膜电图（ERG）反应、外核层（ONL）厚度以及血浆和ROS的脂肪酸组成。采用学生t检验和事后检验的多变量方差分析来确定统计学差异。
喂食FO或SO饲料的大鼠血浆中的n-6/n-3 PUFA比值不同（分别为1.3和62），ROS中的该比值也不同（分别为0.2和1.1）。尽管饲料对血浆脂肪酸组成有显著影响，但在每种饮食方案中，野生型和转基因动物之间只有微小差异。喂食FO的大鼠的ROS中22:6n-3比喂食SO的大鼠多70%，并且野生型的22:6n-3浓度高于转基因动物（野生型>P23H>S334ter）。相反，喂食SO饲料的野生型和转基因大鼠的ROS中22:6n-3水平没有差异。在55日龄时，相对于野生型，两个转基因品系的ERG和ONL厚度均降低。ROS脂肪酸富集对转基因动物的视网膜退化速率没有可检测到的影响。然而，FO饮食对S334ter动物的功能（b波）提供了适度的保护。
给携带视紫红质突变转基因的大鼠喂食n-3脂肪酸可显著提高ROS膜中22:6n-3的水平，但对视网膜退化速率没有影响。因此，退化不是ROS中低（或高）水平的22:6n-3导致的结果，并且在这些遗传性视网膜退化的动物模型中，补充18:3n-3不能挽救即将死亡的光感受器细胞。
