The eye as a gateway to the brain: mechanisms of ocular neuroinvasion by parasitic pathogens

The central nervous system (CNS) is protected by specialized anatomical and immunological barriers that limit pathogen entry; however, several infectious agents have evolved mechanisms to circumvent these defenses. While hematogenous dissemination and peripheral nerve invasion are well-recognized routes of neuroinfection, the eye has received comparatively little attention as a potential gateway to the brain. Owing to its embryological origin from the neuroectoderm, direct anatomical continuity with the CNS through the optic nerve, specialized blood–retinal barrier, and immune-privileged environment, the eye represents a unique neuroimmune interface that may facilitate pathogen persistence and dissemination. Parasitic pathogens, including Toxoplasma (T.) gondii, Acanthamoeba spp., Toxocara spp., Taenia (T.) solium, and Loa (L.) loa, can establish ocular infection and, under certain conditions, contribute to neurological involvement. This review examines the anatomical and immunological features that make the eye a potential neuroinvasive niche and synthesizes current evidence supporting ocular-to-CNS dissemination. Major mechanisms include infected immune-cell trafficking (“Trojan horse” transport), inflammation-induced disruption of the blood–retinal barrier, local neuroinflammatory responses, optic nerve–associated spread, and persistence within ocular reservoirs followed by reactivation. Among currently studied parasites, T. gondii provides the strongest evidence for biologically plausible ocular neuroinvasion, whereas helminths and free-living amoebae highlight additional pathways linking ocular and neurological disease. Although direct proof of ocular-to-brain dissemination remains limited for many pathogens, accumulating experimental and clinical observations support the concept that ocular infection may have broader neurological implications. Understanding the eye–brain interface may improve recognition of neuroinvasive disease and reveal novel targets for therapeutic intervention and prevention.