Constitutive opsin signalling: night blindness or retinal degeneration?
Constitutive opsin signalling: night blindness or retinal degeneration?
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DOI：
10.1016/j.molmed.2004.02.009
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发表时间：
2004-04-01
影响因子：
13.6
通讯作者：
Fain, GL
中科院分区：
文献类型：
--
作者：
Lem, J;Fain, GL
光感受器特异性基因中的一个基因突变子集导致视杆细胞中转导蛋白介导的光信号异常延长激活。在人类和动物模型中，这些突变导致视觉功能障碍，从轻度的静止性夜盲到严重的早发性视网膜变性。在导致夜盲症和视网膜变性的突变之间存在机械差异。在这里，我们假设突变导致视觉级联的连续激活，例如，感光细胞无法再生视紫红质，导致视网膜变性;那些可以终止信号的突变，即使只是部分和间歇性的，足以减缓退化的速度，引起静止性夜盲症。此外，我们推测，细胞内钙离子浓度的持续性激活导致的长期下降是负责触发凋亡杆细胞死亡。
A subset of genetic mutations in photoreceptor-specific genes results in abnormally prolonged activation of transducin-mediated photosignaling in rod cells. In humans and animal models, these mutations cause visual dysfunctions ranging from a mild stationary night blindness to severe, early-onset retinal degeneration. There are mechanistic differences between mutations causing night blindness and those causing retinal degeneration. Here, we hypothesize that mutations causing continuous activation of the visual cascade as the result, for example, of the inability of the photoreceptor to regenerate rhodopsin, lead to retinal degeneration; those mutations that can terminate signaling, even if only partially and intermittently, slow the rate of degeneration sufficiently to give rise to stationary night blindness. Furthermore, we hypothesize that a prolonged decrease in intracellular calcium concentration resulting from persistent activation is responsible for triggering apoptotic rod-cell death.