The effect of ambient titanium dioxide microparticle exposure to the ocular surface on the expression of inflammatory cytokines in the eye and cervical lymph nodes

PURPOSE. To investigate the ocular immune response following exposure to airborne titanium dioxide (TiO2) microparticles. METHODS. Rats in the TiO₂-exposed group (n = 10) were exposed to TiO₂ particles for 2 hours twice daily for 5 days, while the controls (n = 10) were not. Corneal staining score and tear lactic dehydrogenase (LDH) activity were measured to evaluate ocular surface damage, serum immunoglobulin (Ig) G and E were assayed by using enzyme-linked immunosorbent assay, and the size of cervical lymph nodes was measured. In addition, the expression of interleukin (IL)-4, IL-17, and interferon (IFN)-γ in the anterior segment of the eyeball and cervical lymph nodes was measured by immunohistochemistry, real-time reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analysis. RESULTS. Median corneal staining score (3.0), tear LDH activity (0.24 optical density [OD]), and cervical lymph node size (36.9 mm²) were significantly higher in the TiO₂-exposed group than in the control group (1.0, 0.13 OD, and 26.7 mm², respectively). Serum IgG and IgE levels were found to be significantly elevated in the TiO₂-exposed group (P = 0.021 and P = 0.021, respectively). Interleukin 4 expression was increased in the anterior segment of the eyeball and lymph nodes following TiO2 exposure, as measured by immunostaining, real-time RT-PCR, and Western blot. In addition, IL-17 and IFN-γ levels were also increased following TiO₂ exposure compared to controls as measured by immunostaining. CONCLUSIONS. Exposure to airborne TiO₂ induced ocular surface damage. The Type 2 helper Tcell pathway seems to play a dominant role in the ocular immune response following airborne TiO₂ exposure.