Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, Alberta, Canada.
Invest Ophthalmol Vis Sci. 2014 Jan 21;55(1):424-39. doi: 10.1167/iovs.13-13457.
To examine the pattern of cone degeneration in the retina of a transgenic mouse model of Stargartd-like dystrophy (STGD3).
Investigations were performed on ELOVL4/TG1-2 transgenic (TG) mice and wild-type (WT) littermates from 1 to 24 months of age. Phenotypes were assessed by fundus imaging, fatty acid analysis, and electroretinogram (ERG) recording. Cone degeneration pattern was determined on retina whole mounts using immunohistochemistry and Voronoi domain analyses.
Consistent with low transgene expression, photoreceptors degenerate very slowly. At 1 month, anatomical structure and fatty acid composition of the TG retina is comparable with WT. Rod loss appears at 2 months, exhibiting a central to peripheral gradient, and fundus defects are observed at 3 months. In contrast, cone morphology, distribution and function are still normal at 12 months. Cone loss becomes apparent at 15 months when the outer nuclear layer is reduced to 3 to 4 photoreceptor rows. This process starts at the center of the retina and affects cone subtypes similarly. Very few cones remain at 24 months, after all rods have disappeared (18 months). Quantitative studies focusing on cones expressing M-opsin show a net increase in Voronoi domains and a significant decrease in regularity indexes only beyond 15 months.
Photoreceptor degeneration in this STGD3 mouse model follows the time course of a slow rod-cone dystrophy. The cone mosaic is preserved for almost 1 year after the onset of rod loss. This long delay provides an opportunity to examine rod-cone interactions during retinal degeneration and to test therapeutic effectiveness at protracting cone dysfunction.
研究斯塔加特型营养不良（STGD3）转基因小鼠模型中视锥细胞退化的模式。
对 ELOVL4/TG1-2 转基因（TG）小鼠及其同窝野生型（WT）小鼠从 1 至 24 月龄进行研究。通过眼底成像、脂肪酸分析和视网膜电图（ERG）记录评估表型。使用免疫组织化学和 Voronoi 域分析在视网膜全层切片上确定视锥细胞退化模式。
与低转基因表达一致，感光细胞退化非常缓慢。在 1 月龄时，TG 视网膜的解剖结构和脂肪酸组成与 WT 相似。2 月龄时出现视杆细胞丢失，呈中央至周边梯度，3 月龄时出现眼底缺陷。相比之下，在 12 月龄时，视锥细胞形态、分布和功能仍正常。在 15 月龄时，外核层减少到 3 至 4 个感光细胞层时，视锥细胞丢失变得明显。这个过程从视网膜中心开始，对视锥细胞亚型的影响相似。在 24 月龄时，所有视杆细胞消失（18 月龄）后，仅剩下极少数视锥细胞。
该 STGD3 小鼠模型中的感光细胞退化遵循慢型视杆-视锥营养不良的时间进程。在视杆细胞丢失发生后，视锥细胞镶嵌仍能保持近 1 年。这种长时间的延迟为研究视网膜变性过程中的视杆-视锥相互作用以及测试延长视锥细胞功能障碍的治疗效果提供了机会。
