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用于视网膜脂质代谢相关病症的精准药物。

Precision Medicines for Retinal Lipid Metabolism-Related Pathologies.

作者信息

Ana Raquel da, Gliszczyńska Anna, Sanchez-Lopez Elena, Garcia Maria L, Krambeck Karolline, Kovacevic Andjelka, Souto Eliana B

机构信息

UCIBIO-Applied Molecular Biosciences Unit, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.

Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.

出版信息

J Pers Med. 2023 Apr 5;13(4):635. doi: 10.3390/jpm13040635.

Abstract

Oxidation of lipids and lipoproteins contributes to inflammation processes that promote the development of eye diseases. This is a consequence of metabolism dysregulation; for instance, that of the dysfunctional peroxisomal lipid metabolism. Dysfunction of lipid peroxidation is a critical factor in oxidative stress that causes ROS-induced cell damage. Targeting the lipid metabolism to treat ocular diseases is an interesting and effective approach that is now being considered. Indeed, among ocular structures, retina is a fundamental tissue that shows high metabolism. Lipids and glucose are fuel substrates for photoreceptor mitochondria; therefore, retina is rich in lipids, especially phospholipids and cholesterol. The imbalance in cholesterol homeostasis and lipid accumulation in the human Bruch's membrane are processes related to ocular diseases, such as AMD. In fact, preclinical tests are being performed in mice models with AMD, making this area a promising field. Nanotechnology, on the other hand, offers the opportunity to develop site-specific drug delivery systems to ocular tissues for the treatment of eye diseases. Specially, biodegradable nanoparticles constitute an interesting approach to treating metabolic eye-related pathologies. Among several drug delivery systems, lipid nanoparticles show attractive properties, e.g., no toxicological risk, easy scale-up and increased bioavailability of the loaded active compounds. This review analyses the mechanisms involved in ocular dyslipidemia, as well as their ocular manifestations. Moreover, active compounds as well as drug delivery systems which aim to target retinal lipid metabolism-related diseases are thoroughly discussed.

摘要

脂质和脂蛋白的氧化会导致炎症反应,进而促进眼部疾病的发展。这是代谢失调的结果,例如过氧化物酶体脂质代谢功能异常。脂质过氧化功能异常是氧化应激中的关键因素,会导致活性氧诱导的细胞损伤。针对脂质代谢来治疗眼部疾病是一种目前正在被考虑的有趣且有效的方法。事实上,在眼部结构中,视网膜是一个代谢活跃的重要组织。脂质和葡萄糖是光感受器线粒体的燃料底物;因此,视网膜富含脂质,尤其是磷脂和胆固醇。人类布鲁赫膜中胆固醇稳态失衡和脂质积累是与眼部疾病相关的过程,如年龄相关性黄斑变性(AMD)。实际上,针对AMD小鼠模型的临床前试验正在进行,使该领域成为一个有前景的领域。另一方面,纳米技术为开发用于眼部组织的位点特异性药物递送系统以治疗眼部疾病提供了机会。特别是,可生物降解的纳米颗粒是治疗与眼部代谢相关病症的一种有趣方法。在几种药物递送系统中,脂质纳米颗粒具有吸引人的特性,例如无毒理学风险、易于放大以及提高负载活性化合物的生物利用度。本综述分析了眼部血脂异常所涉及的机制及其眼部表现。此外,还对旨在靶向视网膜脂质代谢相关疾病的活性化合物以及药物递送系统进行了深入讨论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5085/10145959/d20ec1bb66df/jpm-13-00635-g001.jpg

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