Laboratorio de Oftalmología Experimental, Facultad de Medicina, Universidad de Murcia, Campus de Espinardo, 30100 Espinardo, Murcia, Spain.
Exp Eye Res. 2010 Dec;91(6):800-10. doi: 10.1016/j.exer.2010.10.003. Epub 2010 Oct 16.
The P23H-1 rat strain carries a rhodopsin mutation frequently found in retinitis pigmentosa patients. We investigated the progressive degeneration of the inner retina in this strain, focussing on retinal ganglion cells (RGCs) fate. Our data show that photoreceptor death commences in the ventral retina, spreading to the whole retina as the rat ages. Quantification of the total number of RGCs identified by Fluorogold tracing and Brn3a expression, disclosed that the population of RGCs in young P23H rats is significantly smaller than in its homologous SD strain. In the mutant strain, there is also RGC loss with age: RGCs show their first symptoms of degeneration at P180, as revealed by an abnormal expression of cytoskeletal proteins which, at P365, translates into a significant loss of RGCs, that may ultimately be caused by displaced inner retinal vessels that drag and strangulate their axons. RGC axonal compression begins also in the ventral retina and spreads from there causing RGC loss through the whole retinal surface. These decaying processes are common to several models of photoreceptor loss, but show some differences between inherited and light-induced photoreceptor degeneration and should therefore be studied to a better understanding of photoreceptor degeneration and when developing therapies for these diseases.
P23H-1 大鼠品系携带一种常发性视网膜色素变性患者的视蛋白突变。我们研究了该品系的内视网膜进行性退化，重点关注视网膜神经节细胞（RGC）的命运。我们的数据表明，感光细胞死亡始于腹侧视网膜，并随着大鼠年龄的增长而扩散到整个视网膜。通过荧光金示踪和 Brn3a 表达对 RGC 总数进行定量，结果表明年轻 P23H 大鼠的 RGC 数量明显少于其同源 SD 品系。在突变品系中，随着年龄的增长也会出现 RGC 丧失：在 P180 时，RGC 就表现出了退行性病变的第一个症状，这可以通过细胞骨架蛋白的异常表达来揭示，而在 P365 时，RGC 则会显著丧失，这可能最终是由移位的内视网膜血管牵拉和绞杀它们的轴突所致。RGC 轴突压迫也始于腹侧视网膜，并从那里扩散，导致整个视网膜表面的 RGC 丧失。这些退化过程在几种光感受器丧失模型中都很常见，但在遗传性和光诱导的光感受器变性之间存在一些差异，因此应该进行研究，以更好地了解光感受器的退化，并在开发这些疾病的治疗方法时进行研究。
