Visual Function in Mice Lacking GM3 Synthase

<b>Purpose</b>: Most complex gangliosides in vertebrates are formed from ganglioside GM3. GM3 deficiency in humans can result in epilepsy and visual impairment. To investigate whether a deficiency of GM3 is involved in visual function, ST3GAL5^−/− mice with mutations in the ST3GAL5 gene-coded GM3 synthase were employed. <b>Materials and Methods</b>: Sixty mice were employed in this study. The glycosphingolipids of mice retinas were analyzed through high performance thin layer chromatography. The morphology of the optic nerves and retinas were evaluated by hematoxylin and eosin staining and immunohistochemical analysis using an anti-glial fibrillary acidic protein (GFAP) antibody. An electroretinogram (ERG) was applied on the eyes of 4, 9, 12, and 14-month-old mice. Also, visual evoked potential (VEP) was applied on 13-month-old mice. <b>Results</b>: The GM3 in the retinas was detected in ST3GAL5^+/+ mice but not ST3GAL5^−/− mice. Also, GM1b and GD1α expressions and lactosylceramide accumulation were found in the ST3GAL5^−/− mouse retinas. There was no significant difference in GFAP expression in the retinas or optic discs between ST3GAL5^+/+ and ST3GAL5^−/− mice. Furthermore, the outcome of ERG and VEP analysis showed no disparity between the two strains in 13 and 14-month-old mice. <b>Conclusion</b>: In the eye, neither histopathological abnormalities nor abnormal functions of the retina were found in GM3-deficient mice. Differing from the situation in patients with GM3 deficiency, the lack of GM3 in mice did not lead to optic nerve atrophy.

**目的**：脊椎动物体内绝大多数复杂神经节苷脂均由神经节苷脂GM3（ganglioside GM3）合成。人类体内GM3缺乏可引发癫痫与视觉障碍。为探究GM3缺乏是否与视觉功能相关，本研究采用了ST3GAL5^−/−小鼠——该小鼠的ST3GAL5基因发生突变，其编码的GM3合酶存在功能缺陷。
**材料与方法**：本研究共使用60只小鼠。通过高效薄层色谱法分析小鼠视网膜中的糖鞘脂；采用苏木精-伊红染色法以及抗胶质纤维酸性蛋白（GFAP）抗体进行免疫组化分析，评估视神经与视网膜的形态学特征。分别对4、9、12及14月龄小鼠的眼部实施视网膜电图（ERG）检测，另对13月龄小鼠实施视觉诱发电位（VEP）检测。
**结果**：ST3GAL5^+/+小鼠的视网膜中可检测到GM3，而ST3GAL5^−/−小鼠视网膜中未检测到GM3。此外，ST3GAL5^−/−小鼠视网膜中可检测到GM1b与GD1α的表达，同时伴有乳糖基神经酰胺的蓄积。ST3GAL5^+/+与ST3GAL5^−/−小鼠的视网膜及视盘的GFAP表达水平无显著差异。进一步的ERG与VEP分析结果显示，13、14月龄的两种品系小鼠间无明显差异。
**结论**：GM3缺乏小鼠的眼部未出现组织病理学异常，亦未检测到视网膜功能异常。与GM3缺乏患者的发病情况不同，小鼠体内GM3缺失并未引发视神经萎缩。