Neuroinflammation and retinal microvascular abnormalities in experimentally-acquired toxoplasmosis in adult C57BL/6 mice: a cellular and molecular dissection

Background: Toxoplasmosis is one of the most frequently identifiable causes of uveitis worldwide. Ocular toxoplasmosis can also lead to retinochoroiditis and vascular occlusions. In this work, we aimed to investigate changes in retinal microvasculature in a mouse model of ocular toxoplasmosis.

Methods: Adult female C57BL/6 mice were intragastrically inoculated with 2 ME49 strain T. gondii cysts and 10, 20, and 30 days post-infection (dpi) body weight and systemic inflammatory profile, retinal, blood flow, leukocyte-endothelium interaction, and inflammatory gene expression were evaluated.

Results: Infected mice displayed a sustained weight loss, independent of chow consumption. Serum TNF-α, IFN-γ, and IL-6 levels were increased at 10 dpi, followed by IL-4 and IL-10 production at 20 dpi. No significant levels of inflammatory markers were observed at 30 dpi. T. gondii infection led to an increase in retinal blood flow and the spontaneously perfused microvessels at all times observed, and a significant increase in structural capillary density at 20 dpi. Retinal blood flow was also significantly increased at 10 and 20 dpi (40 and 80%, respectively), and increased leukocyte-endothelium interaction was observed, with rolling and adhered leukocytes at all studied times. Additionally, infected mice showed endothelial dysfunction in response to topical acetylcholine administration. Microglial marker CX3CR1 was significantly increased at 10 and 30 dpi and Arginase 1, a marker of M2 microglia was increased at 10 dpi.

Conclusions: T. gondii acquired infection leads to an increase in superficial plexus vessel area and capillaries associated with neovascularization, accompanied by an increase in retinal blood flow and neuroinflammation. Our findings demonstrate that ocular toxoplasmosis affects the retinal vasculature, which contributes to visual impairment.