eurekalert.org
Advances in understanding the immune system’s role in ocular diseases are transforming how we address conditions like uveitis, diabetic retinopathy (DR), and age-related macular degeneration (AMD). A recent review by Shengping Hou and colleagues at the Beijing Institute of Ophthalmology delves into the molecular and cellular mechanisms underlying immune-related eye diseases. This review not only broadens our understanding of these complex conditions but also highlights promising therapeutic targets that may lead to safer, more effective treatments in the future.
The review identifies uveitis, the third leading cause of irreversible blindness worldwide, as a condition driven by immune system imbalance. Uveitis results from a disruption between inflammatory mechanisms and regulatory pathways, particularly involving T helper 17 (Th17) cells and regulatory T cells (Tregs). Effector B cells also contribute to inflammation by producing pro-inflammatory cytokines such as interleukin-6 (IL-6), interferon-γ (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF). M1 macrophages, associated with pro-inflammatory responses, further exacerbate the condition.
The overactivation of Th1/Th17 cells, B cells, and M1 macrophages breaks down the blood-retinal barrier, allowing inflammatory cells—such as monocytes, granulocytes, and lymphocytes—to infiltrate the retina and cause tissue destruction. These findings shed light on the intricate immune processes driving the pathogenesis of uveitis.
Dr. Shengping Hou’s team emphasizes the pivotal role of microglia, the retina’s most abundant immune cells, in the development of uveitis. "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," Dr. Hou explains. Their research uncovers a regulatory network influencing immune responses mediated by microglia and their target cells, such as Th17 cells and retinal pigment epithelium (RPE) cells.
The team’s findings also highlight key molecules involved in microglial regulation, including positive regulators like Galectin-3 and YY1 and negative regulators such as NLRP3, FTO, and AhR. These insights establish microglia as critical targets for novel therapeutic strategies aimed at controlling inflammation and preserving ocular health.
Immune-related ocular diseases, including uveitis, DR, AMD, and Graves' ophthalmopathy (GO), are major contributors to blindness worldwide. Current treatments, such as corticosteroids and immunosuppressants, have limited efficacy and pose significant side effects. By identifying specific immune pathways and cells involved in these diseases, researchers are paving the way for precision medicine approaches.
This is especially important for conditions like uveitis, where persistent inflammation can lead to irreversible vision loss. Targeting microglial activity and other immune mechanisms could result in therapies that better control inflammation with fewer side effects, improving patient outcomes and quality of life.
The review also explores the potential of anti-inflammatory strategies and precision therapies in managing immune-related ocular diseases. By targeting immune cells and regulatory networks, future treatments could reduce inflammation and better preserve vision. As Dr. Hou’s work demonstrates, deepening our understanding of the molecular mechanisms underlying these diseases offers a promising path toward safer, more effective interventions.
For healthcare professionals, these findings offer new insights into the immune pathways driving ocular diseases and the therapeutic opportunities they present. This evolving research represents a significant step forward in combating blindness caused by immune-related disorders.