Wild-type cone photoreceptors persist despite neighboring mutant cone degeneration.
Wild-type cone photoreceptors persist despite neighboring mutant cone degeneration.
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DOI：
10.1523/jneurosci.5019-09.2010
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发表时间：
2010-01-06
期刊：
影响因子：
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通讯作者：
Brockerhoff SE
中科院分区：
文献类型：
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作者：
Lewis A;Williams P;Lawrence O;Wong RO;Brockerhoff SE
在许多视网膜疾病中，导致感光细胞丧失的功能障碍仅发生在视杆细胞或视锥细胞中，但变性可以从受影响的细胞类型发展到其健康的邻居。具体而言，在色素性视网膜炎的人类和小鼠模型中，视杆细胞的丧失导致邻近健康视锥细胞的死亡。关于视锥细胞引发的退化及其对邻近细胞的影响，人们知之甚少。有时视杆细胞在视锥细胞死亡后仍然保持正常，而其他患者随着时间的推移会出现暗视觉的丧失。球果死亡对邻近球果的影响尚不清楚。斑马鱼是一种富含视锥细胞的动物模型，其中可以评估死亡视锥细胞杀死邻近健康视锥细胞的潜力。我们以前报道，斑马鱼视锥磷酸二酯酶突变体（pde6cw59）显示快速死亡的锥细胞后不久，他们的形成和随后的损失杆在中央视网膜。在这项研究中，我们研究形态变化与锥体死亡在体内的pde6cw59鱼。然后，我们使用囊胚移植来创建具有混合野生型（WT）和pde6cw59视锥细胞的光感受器层的嵌合鱼。我们发现，死亡的WT锥不会导致相邻的WT锥的损失。WT视锥细胞的存活与移植物的大小和在视网膜内的位置无关。此外，移植的WT视锥细胞在功能失调的突变体视锥细胞最初死亡后至少持续数周。我们的研究结果表明，健康的视锥细胞到受损的视锥细胞的环境中的治疗性移植的潜力。
In many retinal diseases, the malfunction that results in photoreceptor loss occurs only in either rods or cones, but degeneration can progress from the affected cell type to its healthy neighbors. Specifically, in human and mouse models of Retinitis Pigmentosa the loss of rods results in the death of neighboring healthy cones. Significantly less is known about cone-initiated degenerations and their affect on neighboring cells. Sometimes rods remain normal after cone death, whereas other patients experience a loss of scotopic vision over time. The affect of cone death on neighboring cones is unknown. The zebrafish is a cone-rich animal model in which the potential for dying cones to kill neighboring healthy cones can be evaluated. We previously reported that the zebrafish cone phosphodiesterase mutant (pde6cw59) displays a rapid death of cones soon after their formation and a subsequent loss of rods in the central retina. In this study we examine morphological changes associated with cone death in vivo in pde6cw59 fish. We then use blastulae transplantations to create chimeric fish with a photoreceptor layer of mixed wild type (WT) and pde6cw59 cones. We find that the death of inoperative cones does not cause neighboring WT cone loss. The survival of WT cones is independent of transplant size and location within the retina. Furthermore, transplanted WT cones persist at least several weeks after the initial death of dysfunctional mutant cones. Our results suggest a potential for the therapeutic transplantation of healthy cones into an environment of damaged cones.