In the recent “Nature” magazine, a research team from Yale University published the latest research results. They found that the lymphatic system separated inside the eye can mediate eye-brain immunity. When the brain is infected with herpes simplex virus, intravitreal immunity in the eyes can protect the mouse brain from viral attack, and the protective effect is not limited to viral infections. Bacterial infections and tumors can also activate intravitreal immunity to protect the brain.
The back of the eye shares circuits with meningeal lymphatic vessels and has a unified immune response. (photoAC)
Studies have found that there are different lymphatic drainage systems in the front and back of the eye. The back part is connected to the meningeal lymphatic vessels through the lymphatic vessel system in the optic nerve sheath, sharing lymphatic circuits and establishing a unified connection between the back part of the eye and the brain. immune response.
Herpes simplex virus (HSV) is a common cause of fatal encephalitis worldwide, affecting multiple neurological tissues. The researchers inoculated mice with inactivated HSV-2 through four routes: intraperitoneal, intracranial, intraocular anterior chamber, and intravitreal (IVT) to induce systemic immunity and local brain immunity in mice. When mice were re-infected with HSV-2, all mice vaccinated intraperitoneally died of the infection, while intracranial immunization and IVT immunization provided 80% protection for the mice, preliminarily demonstrating the immune response of the eye-brain axis.
The researchers speculate that immune responses in the eye-brain axis are also mediated by regional lymph nodes (LN). By blocking the lymphatic vessels of the deep cervical lymph nodes (dCLN), the protective effect provided by IVT immunity disappears. IVT immunization can also promote the differentiation of B cells in the germinal center of dCLN and significantly increase the level of antigen-specific CD4+ T cells in dCLN.
After vaccination with inactivated HSV-2, all immunization routes caused an increase in serum anti-HSV-2 antibody levels, but only intracranial immunization and IVT immunized mice could detect anti-HSV-2 antibodies in the cerebrospinal fluid, indicating that serum antibodies It does not mediate immune protection of the central nervous system, but IVT immunity mediates protection of the central nervous system through local antibody-dependent responses.
Not only that, the researchers found that IVT can also produce eye-brain immune responses to a variety of pathogens in addition to HSV-2, such as HSV-1 and Streptococcus pneumoniae, the latter being the main pathogen of bacterial meningitis; even if intracranial In the case of tumors, immunization via IVT or intracranial routes may also provide protection. Of course, the immune pathway and its protective effect are related to the type of infection or tumor. For example, in cutaneous melanoma models, subcutaneous immunization is more effective than intracranial or IVT immunization.
Immunity (pixabay)
Next, the researchers explored the mechanism of eye-brain immunity. Injecting fluorescently labeled dextran into the anterior chamber or IVT of mice’s eyes revealed a separate drainage system between the anterior chamber and vitreous body. Continuing to label the lymphatic network associated with the optic nerve, the researchers observed that the lymphatic vasculature is located on the membrane surrounding the nerve, rather than the nerve itself, and that lymphatic vessels are present in the mouse optic nerve sheath, using fluorescent tracers and antibodies injected via the IVT route. It can enter the optic nerve sheath lymphatic vessels through cerebrospinal fluid, and vascular endothelial growth factor C (VEGFC) can increase IVT drainage.
The researchers also found that ocular lymphatic drainage is critical to the immune response to gene therapy, and that injection of recombinant adeno-associated virus behind the eye can induce an immune response more effectively.
Collectively, the study demonstrates that the posterior compartment of the eye has a unique lymphatic drainage system that interfaces with the central nervous system meningeal lymphatic network at the dCLN and the optic nerve sheath lymphatic network that can drain antigens inoculated into the vitreous to the dCLN and in the brain Initiate local protective immune response.
The research team is trying to use eye injections to treat leaky retinal blood vessels common in patients with macular edema, diabetes and glaucoma. “Since there is a common immune response between the brain and the eye,” the authors said, “the eye is much easier to treat than the brain.”
2024-03-15 10:24:51
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