Bruch's Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration.
Bruch's Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration.
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DOI：
10.3390/jcm12082870
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发表时间：
2023-04-14
影响因子：
3.9
通讯作者：
Steel, David H.
中科院分区：
文献类型：
--
作者：
Hammadi, Sarah;Tzoumas, Nikolaos;Ferrara, Mariantonia;Meschede, Ingrid Porpino;Lo, Katharina;Harris, Claire;Lako, Majlinda;Steel, David H.
关键词：
补体系统对于免疫监视至关重要，提供了身体对抗病原体的第一道防线。然而，其监管机构的不平衡可能导致不适当的过度激活，导致年龄相关性黄斑变性（AMD）等疾病，这是全球影响约2亿人的不可逆失明的主要原因。AMD中的补体激活被认为开始于脉络膜毛细血管，但它也在视网膜下和视网膜色素上皮（RPE）空间中起关键作用。Bruch膜（BrM）充当视网膜/RPE和脉络膜之间的屏障，阻碍补体蛋白扩散。这种障碍随着年龄和AMD而增加，导致补体激活的区室化。在这篇综述中，我们全面研究了BrM的结构和功能，包括通过体内成像可见的年龄相关变化，以及补体功能障碍对AMD发病机制的影响。我们还探讨了各种递送途径（全身、玻璃体内、视网膜下和脉络膜上）的潜力和局限性，以安全有效地递送常规和基于基因治疗的补体抑制剂来治疗AMD。需要进一步的研究来了解补体蛋白在BrM中的扩散，并优化对视网膜的治疗。
The complement system is crucial for immune surveillance, providing the body’s first line of defence against pathogens. However, an imbalance in its regulators can lead to inappropriate overactivation, resulting in diseases such as age-related macular degeneration (AMD), a leading cause of irreversible blindness globally affecting around 200 million people. Complement activation in AMD is believed to begin in the choriocapillaris, but it also plays a critical role in the subretinal and retinal pigment epithelium (RPE) spaces. Bruch’s membrane (BrM) acts as a barrier between the retina/RPE and choroid, hindering complement protein diffusion. This impediment increases with age and AMD, leading to compartmentalisation of complement activation. In this review, we comprehensively examine the structure and function of BrM, including its age-related changes visible through in vivo imaging, and the consequences of complement dysfunction on AMD pathogenesis. We also explore the potential and limitations of various delivery routes (systemic, intravitreal, subretinal, and suprachoroidal) for safe and effective delivery of conventional and gene therapy-based complement inhibitors to treat AMD. Further research is needed to understand the diffusion of complement proteins across BrM and optimise therapeutic delivery to the retina.
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影响因子：
4.4
作者：
Bora, Nalini S.;Kaliappan, Sankaranarayanan;Bora, Puran S.
通讯作者：
Bora, Puran S.
影响因子：
4.4
作者：
Annamalai B;Parsons N;Nicholson C;Obert E;Jones B;Rohrer B
通讯作者：
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影响因子：
3.9
作者：
BILL, A;SPERBER, GO
通讯作者：
SPERBER, GO
影响因子：
4.6
作者：
Armento, Angela;Honisch, Sabina;Ueffing, Marius
通讯作者：
Ueffing, Marius
从体内腺病毒表达的可溶性CD59是对鼠肝血管内皮的补体沉积的有效抑制剂。
影响因子：
3.7
作者：
Gandhi J;Cashman SM;Kumar-Singh R
通讯作者：
Kumar-Singh R