Sanyal S, Jansen H
Department of Anatomy, Faculty of Medicine, Erasmus University, Rotterdam, The Netherlands.
Prog Clin Biol Res. 1989;314:233-50.
In the developing retina of homozygous rd/rd mutant mice the time of onset of degenerative changes and the period of rapid photoreceptor cell loss overlaps the later phase of differentiation during which the maturation of the receptors and the completion of the synaptic connections take place. It remains unresolved if the retarded synaptogenesis within the photoreceptor terminals of the rod cells is a direct effect of the mutant gene or an indirect consequence of premature cell death. In the retina of homozygous rds/rds mutant mice early indication of gene expression within the photoreceptor cells is also recorded as photoreceptor outer segments fail to develop. However, during the very slow rate of degeneration, the surviving cells develop normal synaptic contacts within their terminals. Furthermore, some of the rod cells, though not the cones, go on to enlarge their synaptic structures as more and more photoreceptor cells are lost. In the retina of double homozygous mutant rd/rd;rds/rds mice the photoreceptor cells remain lacking in outer segments, as would be expected, but curiously enough, survive longer than in the rd/rd retina. Among this population of photoreceptor cells with extended life-span profiles of rod terminals are frequently encountered which contain a normal synaptic structure - one synaptic ribbon with two laterally placed processes of horizontal cells and one medially facing process of a bipolar cell. A number of these terminals also show signs of synaptic enlargement. Thus it can be concluded that some of the terminals of the rod photoreceptor cells of the double homozygous rd/rd,rds/rds mice, which survive longer than in the rd/rd mice, develop synapses that are either comparable to normal or resemble those of the rds/rds retina. These findings suggest that retarded synaptogenesis within the rod terminals of the rd/rd retina is likely to result from a pathogenic defect affecting the whole cell and is not due to a specific or exclusive action of the mutant gene on the synaptic components involved.
在纯合 rd/rd 突变小鼠发育中的视网膜中，退行性变化的起始时间和光感受器细胞快速丢失的时期与分化的后期重叠，在此期间受体成熟和突触连接完成。目前仍未解决的问题是，视杆细胞光感受器终末内突触发生延迟是突变基因的直接作用还是细胞过早死亡的间接后果。在纯合 rds/rds 突变小鼠的视网膜中，由于光感受器外段未能发育，也记录到了光感受器细胞内基因表达的早期迹象。然而，在非常缓慢的退化过程中，存活的细胞在其终末形成了正常的突触联系。此外，随着越来越多的光感受器细胞丢失，一些视杆细胞（而非视锥细胞）继续扩大其突触结构。在双纯合突变 rd/rd;rds/rds 小鼠的视网膜中，如预期的那样，光感受器细胞仍然缺乏外段，但奇怪的是，它们的存活时间比 rd/rd 视网膜中的细胞更长。在这群具有延长寿命的视杆终末的光感受器细胞中，经常可以看到含有正常突触结构的细胞——一个突触带，有两个水平细胞横向放置的突起和一个双极细胞朝向内侧的突起。许多这些终末也显示出突触扩大的迹象。因此可以得出结论，双纯合 rd/rd,rds/rds 小鼠的视杆光感受器细胞的一些终末，其存活时间比 rd/rd 小鼠中的终末更长，形成的突触要么与正常突触相当，要么类似于 rds/rds 视网膜中的突触。这些发现表明，rd/rd 视网膜视杆终末内突触发生延迟可能是由于影响整个细胞的致病缺陷所致，而不是由于突变基因对所涉及的突触成分的特异性或排他性作用。
