Pharmacological approaches to retinitis pigmentosa: A laboratory perspective
Pharmacological approaches to retinitis pigmentosa: A laboratory perspective
复制标题
DOI：
10.1016/j.preteyeres.2015.06.005
复制
发表时间：
2015-09-01
影响因子：
17.8
通讯作者：
Strettoi, Enrica
中科院分区：
文献类型：
--
作者：
Guadagni, Viviana;Novelli, Elena;Strettoi, Enrica
视网膜光感受器是高度特化和执行神经元。它们的细胞结构被精巧地设计成容纳高浓度的分子，这些分子参与光捕获、光转导、电和化学信号传导、膜和分子周转、光和暗适应、网络活动等。这种高效率和分子复杂性需要很大的代谢需求，总共赋予光感受器对外部和内部损伤的特殊敏感性，其发生通常导致这些细胞的退化和失明。在视网膜色素变性中，视网膜中表达的基因中的大量突变和编码大量蛋白质导致光感受器的进行性死亡和失明。分子工具的最新进展极大地促进了RP的潜在遗传学和分子基础的鉴定，从而成功地对某些类型的突变实施基因治疗，并在人类患者中恢复视力。然而，RP的遗传异质性使得突变独立的方法非常可取的，虽然许多障碍铺平了道路，为治疗这种复杂的疾病，这仍然orphan.The审查的一般策略将集中在治疗RP的药理学工具的基础上，选择，在许多正在进行的研究中，依赖于强有力的实验证据或理由的方法。对于前瞻性治疗，可以预见新的概念将出现在基础研究中，阐明将原发性突变与感光细胞死亡连接起来的途径，可能揭示药物干预的共同分子靶点。(C)2015爱思唯尔有限公司版权所有。
Retinal photoreceptors are highly specialized and performing neurons. Their cellular architecture is exquisitely designed to host a high concentration of molecules involved in light capture, phototransduction, electric and chemical signaling, membrane and molecular turnover, light and dark adaption, network activities etc. Such high efficiency and molecular complexity require a great metabolic demand, altogether conferring to photoreceptors particular susceptibility to external and internal insults, whose occurrence usually precipitate into degeneration of these cells and blindness. In Retinitis Pigmentosa, an impressive number of mutations in genes expressed in the retina and coding for a large varieties of proteins leads to the progressive death of photoreceptors and blindness. Recent advances in molecular tools have greatly facilitated the identification of the underlying genetics and molecular bases of RP leading to the successful implementation of gene therapy for some types of mutations, with visual restoration in human patients. Yet, genetic heterogeneity of RP makes mutation-independent approaches highly desirable, although many obstacles pave the way to general strategies for treating this complex disease, which remains orphan.The review will focus on treatments for RP based on pharmacological tools, choosing, among the many ongoing studies, approaches which rely on strong experimental evidence or rationale. For perspective treatments, new concepts are foreseen to emerge from basic studies elucidating the pathways connecting the primary mutations to photoreceptor death, possibly revealing common molecular targets for drug intervention. (C) 2015 Elsevier Ltd. All rights reserved.