Remodeling of cone photoreceptor cells after rod degeneration in rd mice.

Remodeling of cone photoreceptor cells after rod degeneration in rd mice.
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DOI:
10.1016/j.exer.2008.11.022
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发表时间:
2009-03
影响因子:
3.4
通讯作者:
Strettoi, Enrica
Strettoi, Enrica
中科院分区:
医学3区
文献类型:
--
作者:
Lin, Bin;Masland, Richard H.;Strettoi, Enrica

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我们研究了 rd 小鼠视杆细胞退化后视锥细胞的存活情况。用腺相关病毒 (AAV) 载体转导后,通过选择性表达绿色荧光蛋白 (GFP) 来可视化视锥细胞。正如之前报道的,许多视锥细胞在视杆细胞最初退化后仍然存活。在最初的退化之后不久,它们失去了外部节段,除了残留的内部节段外,它们全部失去了。并且它们部分缩回或失去轴突和突触蒂。然而,它们保留了锥体表型的许多基本特征,并且在数周内显示出表明过程大量再生的极化形态。细胞保持其层状位置,在薄得多的外丛状层远端形成细胞行。随后体细胞增大。大多数细胞延伸了双极过程,重建了感光细胞的原始双极形态——尽管现在相对于原始位置转向了一侧。这些细胞表达短波或中波视蛋白、恢复蛋白和连接蛋白 36。一个或多个极化过程通常可以显示包含突触带,如 RIBEYE 抗体所显示的那样。视锥细胞不表达蛋白激酶 C α、Go α、ChX10 或钙结合蛋白(双极或水平细胞的标记物)。部分分化的锥体形态持续至少几个月,之后突起开始缩回并且细胞缓慢损失。因此,在失去视杆细胞主导的微环境后,视锥细胞达到半稳定状态,其中大部分正常表型得以保留。人类 RP 供体视网膜中的视锥光感受器从其形态来看似乎经历了类似的进展。拯救视锥细胞的治疗窗口可能比想象的要长。
We studied the survival of cone photoreceptors following the degeneration of rods in the rd mouse. Cones were visualized by selective expression of green fluorescent protein (GFP) following transduction with an adeno-associated virus (AAV) vector. As previously reported, many cones survive after the initial degeneration of the rods. Soon after the initial degeneration, they lose their outer segments and all but a vestigial inner segment; and they partially retract or lose their axon and synaptic pedicle. However, they retain many fundamental features of the cone phenotype, and for many weeks show a polarized morphology indicative of substantial regrowth of processes. The cells retain their laminar position, forming a cell row just distal to a much thinned outer plexiform layer. The somata subsequently enlarge. Most of the cells extend bipolar processes, recreating the original bipolar morphology of a photoreceptor cell -- though now turned on its side relative to the native position. The cells express short- or middle– wavelength opsins, recoverin and connexin 36. One or more of the polarized processes could often be shown to contain synaptic ribbons, as visualized by antibodies against RIBEYE. The cones do not express protein kinase C alpha, Go alpha, ChX10 or calbindin, markers of bipolar or horizontal cells. The partially differentiated cone morphology persists for at least several months, after which the processes begin to retract and there is slow loss of the cells. Thus, during the time following the loss of their rod-dominated microenvironment, the cones achieve a semi-stable state in which much of their normal phenotype is preserved. Cone photoreceptors in retinas of human RP donors appear from their morphology to undergo a similar progression. The therapeutic window for rescue of cone photoreceptors may be longer than would have been thought.
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