Nishikawa S, LaVail M M
Beckman Vision Center, University of California San Francisco, San Francisco, CA, 94143-0730, USA.
Exp Eye Res. 1998 Nov;67(5):509-15. doi: 10.1006/exer.1998.0538.
Neovascularization (NV) of the retinal pigment epitheium (RPE) by retinal capillaries following degeneration and loss of photoreceptor cells is a widely recognized phenomenon in rodents. NV of the RPE usually occurs several weeks to months after the loss of photoreceptor cells. We have observed that NV of the RPE occurs much earlier in a line of P23H mutant rhodopsin transgenic mice than in most other mice and rats that have been previously examined. To compare the temporal course of RPE NV in P23H mice with that of two other retinal degeneration mutants with the same time course of photoreceptor cell loss, we have quantified the number of retinal capillaries in the RPE of P23H and Q344ter mutant rhodopsin transgenic mice and retinal degeneration (rd/rd) mice at ages ranging from postnatal day (P) 20-400. Retinal capillary profiles located within the RPE were already present as early as P20 in the P23H retinas, and although these usually were located where most photoreceptor nuclei were missing, they occasionally were found where 1-2 rows of photoreceptor nuclei were still present. The maximal incidence was found in P23H retinas at P100. By contrast, NV of the RPE in rd/rd and Q344ter mice occurred much later. In rd/rd, a significant number of capillary profiles was not seen in the RPE until about P130, and not until about P180 in Q344ter. Both showed maximal incidence at about P240. In all three mutants, an apparent regression of the capillaries occurred following the peak, with that in the P23H mice preceeding the other two mutants. The findings suggest that the P23H mutant rhodopsin transgenic mouse may be a useful model for studying the regulation of NV in the outer retina.
在啮齿动物中,光感受器细胞变性和丧失后,视网膜毛细血管对视网膜色素上皮(RPE)的新生血管化(NV)是一种广泛认可的现象。RPE的NV通常发生在光感受器细胞丧失后的数周或数月。我们观察到,在P23H突变视紫红质转基因小鼠品系中,RPE的NV比之前检测的大多数其他小鼠和大鼠发生得更早。为了比较P23H小鼠与另外两个具有相同光感受器细胞丧失时间进程的视网膜变性突变体中RPE NV的时间进程,我们对出生后第(P)20 - 400天的P23H和Q344ter突变视紫红质转基因小鼠以及视网膜变性(rd/rd)小鼠的RPE中的视网膜毛细血管数量进行了量化。位于RPE内的视网膜毛细血管轮廓早在P20时就在P23H视网膜中出现,尽管这些通常位于大多数光感受器细胞核缺失的部位,但偶尔也会在仍有1 - 2排光感受器细胞核的部位发现。最大发生率在P100时出现在P23H视网膜中。相比之下,rd/rd和Q344ter小鼠中RPE的NV发生得要晚得多。在rd/rd中,直到约P130才在RPE中看到大量的毛细血管轮廓,而在Q344ter中直到约P180才看到。两者都在约P240时显示出最大发生率。在所有三个突变体中,毛细血管在达到峰值后都出现了明显的消退,P23H小鼠中的消退先于其他两个突变体。这些发现表明,P23H突变视紫红质转基因小鼠可能是研究外视网膜NV调节的有用模型。