In-depth exploration of ocular immune diseases: From molecular mechanisms to novel therapies？

This study is led by Shengping Hou (Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University). The eyes have long been regarded as "immune-privileged" organs. Immunological system of ocular tissues prevents or resolves inflammation and maintain homeostasis. Aberrant activation of the immune system induces autoimmunity, which affects the ocular and its surrounding tissues in certain extend. Ocular immune-related diseases are a category of eye diseases caused by abnormal immune inflammatory responses, and they are one of the leading causes of blindness with high incidence. This comprehensive review delves into the molecular and cellular mechanisms underlying a spectrum of conditions driven by immune system dysregulation, including uveitis, diabetic retinopathy (DR), age-related macular degeneration (AMD), and Graves' ophthalmopathy (GO). The review highlights the different types of immune cells, inflammatory mediators, and associated signaling pathways that are involved in the pathophysiology of these ophthalmopathies, which is beneficial for broadening our comprehension of the intricate mechanisms underlying in ocular immune diseases.

Cellular mechanisms of immune response are playing an increasingly important role in the pathogenesis of immune-related ocular diseases. In addition to T and B cells, the roles of microglia and other macrophages are being increasingly investigated. “Our group focus on the study of uveitis, which is the third leading cause of irreversible blindness worldwide, characterized by the disruption of ocular immune homeostasis and persistent inflammatory responses. In the past years, our team has been dedicated to studying the role of microglia in the pathogenesis of uveitis and the development of treatment methods. We have found that microglia are the most abundant immune cells in the retina, and play an indispensable role in the occurrence of uveitis, which can be an important target cell for the prevention and treatment research of the disease. We first reveal the presence of disease-associated CD74⁺Ccl5⁺ microglial cell subsets in uveitis, providing new target cells for the precise prevention and treatment of this disease. We also elucidated the regulatory network and mechanism of immune responses mediated by microglia and their target cells Th17 and RPE. A series of work has been carried out around the immune regulation of microglia, revealing a regulatory network composed of negative regulatory molecules such as NLRP3, FTO, AhR, and positive regulatory molecules such as Galectin-3, YY1, Ikzf1,” said Dr. Shengping Hou.

In this review, they have chosen to discuss uveitis, DR, AMD, and GO due to the pivotal role that immune factors play in their pathogenesis. Interventions targeting these immune mechanisms have shown to yield positive therapeutic effects on these diseases. The clinical implications of their research are profound. By understanding the molecular mechanisms, the team aims to develop specific, safe, and effective treatment strategies that can improve patient outcomes. This is particularly important given that current treatments, such as corticosteroids and immunosuppressants, have limited efficacy and significant side effects. They also discuss the future directions of utilizing anti-inflammatory regimes in the management of these diseases, which will facilitate a better understanding of the pathogenesis of immune-related ocular diseases and provide new insights for future treatment approaches.

See the article:

Ocular immune-related diseases: Molecular Mechanisms and Therapy

https://doi.org/10.1002/mco2.70021