Impaired formation of the inner retina in an AChE knockout mouse results in degeneration of all photoreceptors
Impaired formation of the inner retina in an AChE knockout mouse results in degeneration of all photoreceptors
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DOI：
10.1111/j.1460-9568.2004.03753.x
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发表时间：
2004-12-01
影响因子：
3.4
通讯作者：
Layer, PG
中科院分区：
文献类型：
--
作者：
Bytyqi, AH;Lockridge, O;Layer, PG
致盲性疾病主要归因于光感受器/色素上皮复合体的遗传缺陷。作为一种替代方案，我们在这里显示的乙酰胆碱酯酶（AChE）基因敲除小鼠，感光细胞变性后受损的发展的内层视网膜。在出生后的前15天的AChE（-/-）视网膜，三个主要calretinin亚层的内丛状层（IPL）的干扰。因此，无长突和神经节细胞的过程在整个IPL中弥漫性地交叉。相比之下，小清蛋白细胞呈现非层状IPL模式在野生型，但在乙酰胆碱酯酶（-/-）小鼠的过程中成为结构化的两个“新的”sublaminae。在这个早期阶段，光感受器在AChE（-/-）视网膜中以正常速率规则排列。然而，在接下来的75天，首先是它们的外节，然后是整个感光层完全退化的细胞凋亡。最终，内层视网膜的细胞也经历凋亡。由于丁酰胆碱酯酶（BChE）在AChE（-/-）小鼠中处于正常水平，因此观察到的效应必须完全是由于AChE缺失所致。这些是第一个在体内的研究结果，以显示AChE在视网膜内部网络的形成中的决定性作用，当缺乏时，最终导致感光细胞变性。
Blinding diseases can be assigned predominantly to genetic defects of the photoreceptor/pigmented epithelium complex. As an alternative, we show here for an acetylcholinesterase (AChE) knockout mouse that photoreceptor degeneration follows an impaired development of the inner retina. During the first 15 postnatal days of the AChE(-/-) retina, three major calretinin sublaminae of the inner plexiform layer (IPL) are disturbed. Thereby, processes of amacrine and ganglion cells diffusely criss-cross throughout the IPL. In contrast, parvalbumin cells present a nonlaminar IPL pattern in the wild-type, but in the AChE(-/-) mouse their processes become structured within two 'novel' sublaminae. During this early period, photoreceptors become arranged regularly and at a normal rate in the AChE(-/-) retina. However, during the following 75 days, first their outer segments, and then the entire photoreceptor layer completely degenerate by apoptosis. Eventually, cells of the inner retina also undergo apoptosis. As butyrylcholinesterase (BChE) is present at a normal level in the AChE(-/-) mouse, the observed effects must be solely due to the missing AChE. These are the first in vivo findings to show a decisive role for AChE in the formation of the inner retinal network, which, when absent, ultimately results in photoreceptor degeneration.