Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, Pavia, Italy.
Department of Ophthalmology, Faculty of Medical Sciences in Katowice, Medical University of Silesia in Katowice, Katowice, Poland; GlaucoTech Co., Katowice, Poland.
J Control Release. 2024 Jan;365:448-468. doi: 10.1016/j.jconrel.2023.11.035. Epub 2023 Dec 2.
Nanoscale extracellular vesicles (EVs), consisting of exomers, exosomes and microvesicles/ectosomes, have been extensively investigated in the last 20 years, although their biological role is still something of a mystery. EVs are involved in the transfer of lipids, nucleic acids and proteins from donor to recipient cells or distant organs as well as regulating cell-cell communication and signaling. Thus, EVs are important in intercellular communication and this is not limited to sister cells, but may also mediate the crosstalk between different cell types even over long distances. EVs play crucial functions in both cellular homeostasis and the pathogenesis of diseases, and since their contents reflect the status of the donor cell, they represent an additional valuable source of information for characterizing complex biological processes. Recent advances in isolation and analytical methods have led to substantial improvements in both characterizing and engineering EVs, leading to their use either as novel biomarkers for disease diagnosis/prognosis or even as novel therapies. Due to their capacity to carry biomolecules, various EV-based therapeutic applications have been devised for several pathological conditions, including eye diseases. In the eye, EVs have been detected in the retina, aqueous humor, vitreous body and also in tears. Experiences with other forms of intraocular drug applications have opened new ways to use EVs in the treatment of retinal diseases. We here provide a comprehensive summary of the main in vitro, in vivo, and ex vivo literature-based studies on EVs' role in ocular physiological and pathological conditions. We have focused on age-related macular degeneration, diabetic retinopathy, glaucoma, which are common eye diseases leading to permanent blindness, if not treated properly. In addition, the putative use of EVs in retinitis pigmentosa and other retinopathies is discussed. Finally, we have reviewed the potential of EVs as therapeutic tools and/or biomarkers in the above-mentioned retinal disorders. Evidence emerging from experimental disease models and human material strongly suggests future diagnostic and/or therapeutic exploitation of these biological agents in various ocular disorders with a good possibility to improve the patient's quality of life.
纳米级细胞外囊泡 (EVs) 包括外泌体、外核体和微囊泡/质膜小泡，在过去 20 年中得到了广泛研究，尽管它们的生物学功能仍然是一个谜。EVs 参与脂质、核酸和蛋白质从供体细胞到受体细胞或远处器官的转移，以及调节细胞间通讯和信号转导。因此，EVs 在细胞间通讯中起着重要作用，这种通讯不仅限于姐妹细胞，还可能介导不同细胞类型之间的串扰，甚至在长距离内进行。EVs 在细胞稳态和疾病发病机制中发挥着至关重要的作用，并且由于其内容反映了供体细胞的状态，因此它们代表了用于表征复杂生物过程的另一种有价值的信息来源。分离和分析方法的最新进展导致了对 EVs 的表征和工程的实质性改进，从而导致它们被用作疾病诊断/预后的新型生物标志物，甚至被用作新型治疗方法。由于其携带生物分子的能力，已经设计了各种基于 EV 的治疗应用来治疗几种病理状况，包括眼部疾病。在眼睛中，已经在视网膜、房水、玻璃体和泪液中检测到 EVs。其他形式的眼内药物应用的经验为 EV 在治疗视网膜疾病中的应用开辟了新途径。我们在这里提供了关于 EV 在眼部生理和病理条件中的作用的主要基于体外、体内和离体文献的综述。我们重点关注年龄相关性黄斑变性、糖尿病性视网膜病变、青光眼，这些疾病如果不及时治疗，会导致永久性失明。此外，还讨论了 EV 在视网膜色素变性和其他视网膜病变中的潜在用途。最后，我们回顾了 EV 作为上述视网膜疾病的治疗工具和/或生物标志物的潜力。来自实验疾病模型和人体材料的证据强烈表明，未来可以利用这些生物制剂在各种眼部疾病中进行诊断和/或治疗，有可能改善患者的生活质量。
