生物材料在眼部治疗中调节先天免疫反应中的作用

Mehrnoosh Rafiei, Jin Teng Chung, Y. Chau
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摘要

眼睛是一个难以治疗的器官,因为它的再生能力差,容易发炎;因此,它具有免疫特权机制。在眼部退行性疾病的情况下,慢性和不受控制的眼部炎症可以克服这种免疫反应,引发并加剧组织退化,最终导致失明。最近关于眼部先天免疫系统在调节急性和慢性炎症以及组织纤维化和稳态中的关键作用的里程碑式发现,阐明了新的治疗干预措施在分子、细胞和组织水平上调节眼部免疫反应的价值。这种策略可以通过使用治疗剂靶向常驻吞噬细胞和抗原呈递细胞,即小胶质细胞和树突状细胞,以及浸润的中性粒细胞和巨噬细胞来实现。生物材料是宿主的外来物质,与先天免疫细胞相互作用。为了利用这种内在的免疫调节特性,生物材料,如植入物、注射库和纳米/微米颗粒,可以单独用作治疗,或者与不同的有效载荷一起用作免疫相关眼部疾病的载体。本文讨论了生物降解性、大小、形状和电荷等物理化学性质如何影响生物材料与眼睛先天免疫系统的相互作用,从而影响促炎或抗炎反应的结果。设计耐受性生物材料需要了解眼睛的免疫反应,包括人工晶状体、细胞支架、治疗分子库或基因疗法载体。这篇综述中的讨论将阐明生物材料的潜在用途,将免疫反应导向有利的治疗结果。
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Roles of biomaterials in modulating the innate immune response in ocular therapy
The eye is a hard-to-treat organ due to its poor regenerative capacity and susceptibility to inflammation; as a result, it has an immune privilege mechanism. In the case of ocular degenerative disorders, chronic and uncontrolled ocular inflammations can overcome this immune response to initiate and exacerbate tissue degeneration, ultimately leading to blindness. Recent landmark discoveries on the key roles of the ocular innate immune system in regulating acute and chronic inflammations as well as tissue fibrosis and homeostasis have shed light on the value of novel treatment interventions in modulating ocular immune responses at the molecular, cellular, and tissue levels. This strategy can be attained by using therapeutics to target resident phagocytes and antigen-presenting cells, namely, microglia and dendritic cells, as well as infiltrating neutrophils and macrophages. Biomaterials are foreign materials to the host and interact with innate immune cells. To leverage such intrinsic immunomodulatory properties, biomaterials such as implants, injectable depots, and nano/micro particles can be used alone as a treatment or with different payloads as carriers in immune-related ocular disorders. This article discusses how physicochemical properties such as biodegradability, size, shape, and charge affect biomaterials’ interaction with the eye’s innate immune system, therefore influencing outcomes towards pro- or anti-inflammatory responses. Knowledge about the eye’s immunological response is required for designing tolerogenic biomaterials including intraocular lenses, cellular scaffolds, therapeutic molecule depots, or carriers of gene therapies. The discussion presented in this review will shed light on the potential use of biomaterials to direct immune responses toward favorable treatment outcomes.
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