The eye maintains immune privilege through the blood-retinal barrier and immunosuppressive factors, which prevent excessive inflammation while preserving vision. Skewed immune responses, including activation of T cells, B cells, and microglia, lead to inflammation and tissue damage and contribute to diseases such as uveitis, diabetic retinopathy, age-related macular degeneration, and Graves’ ophthalmopathy.
A comprehensive review, published in MedComm, explored the molecular mechanisms, immune responses, and therapeutic strategies for these diseases and provided an overview of the roles of immune cells, cytokines, and signaling pathways in their pathogenesis, as well as the growing potential of immunotherapy.
In uveitis, T helper cells, particularly Th1 and Th17, drive inflammation through cytokines IFN-γ and IL-17. Regulatory T cells (Tregs) help resolve inflammation and restore immune homeostasis. Corticosteroids remain the first-line treatment but are limited by side effects. Biologics such as TNF inhibitors and agents that target IL-17 and IL-23 pathways offer alternative strategies.
Elevated levels of IL-17 and VEGF from microglia and macrophages exacerbate neovascularization and inflammation in diabetic retinopathy (DR). Anti-VEGF agents are standard but have limitations in addressing inflammation. New approaches include targeting microglial activation and polarization.
Excessive immune activation, driven by T cells and macrophage polarization, contributes to age-related macular degeneration (AMD) progression. Like DR, anti-VEGF therapies are the norm for wet AMD, but anti-inflammatory agents and complement inhibitors are emerging for both wet and dry AMD.
T cells and B cells interact with orbital fibroblasts in Graves’ ophthalmopathy (GO), leading to inflammation, fibrosis, and adipogenesis. Like uveitis, key cytokines in GO include IFN-γ and IL-17, plus IL-6. Corticosteroids and biologics including TNF inhibitors and teprotumumab (an IGF-1R inhibitor) show promise in managing inflammation and orbital tissue remodeling.
“The application of immunotherapy in ocular immune diseases holds broad prospects,” the researchers concluded, describing personalized medicine and gene-editing technology. Further studies may address efficacy, safety, and best practices for incorporating new therapies into clinical workflows, such as optimized dosing and schedules.
A full list of author disclosures can be found in the published research.
