Meibomian Gland IL-17 Expression Is Associated with Gland Dysfunction Following Corneal Nerve Injury

To investigate the impact of corneal nerve injury on meibomian glands (MG) and elucidate underlying mechanisms.

Using a murine unilateral corneal trephination model, we evaluated nerve density (βIII-tubulin), MG lipogenesis, cytokine expression (IL-1β, IL-6, TNF-α, IL-17), inflammatory cell infiltration, and apoptosis at 2 weeks. Inflammatory cells in tarsal plates and effector T cells in eye-draining lymph nodes (DLN) were quantified by flow cytometry. Human MG epithelial cells (HMGECs) were treated with IL-17 to assess lipogenic genes, PPAR-γ, pAkt/Akt, and inflammatory markers. IL-17 was blocked in vivo by intraperitoneal injection. In humans, MG function was compared between post-refractive surgery patients and age-matched controls.

Trephined eyes showed reduced nerve density and lipogenesis with increased apoptosis and CD45⁺ cell infiltration at 2 weeks, without significant increases in CD4⁺IFN-γ⁺ or CD4⁺IL-17⁺ T cells in DLN. Immunohistochemistry showed increased MG IL-17 expression, whereas IL-1β, IL-6, and TNF-α were unchanged. CD45^-IL-17⁺ cells, rather than CD45⁺IL-17⁺ cells, were increased in tarsal plates. In vitro, IL-17 treatment decreased cell viability and the pAkt/Akt ratio at intermediate status, suppressed FABP4 gene expression and PPAR-γ protein, and upregulated CXCL2, IL-1β, and IL-8 in differentiated cells. In vivo IL-17 blockade reduced CD45⁺ cell infiltration and restored lipogenesis. In humans, 30 post-refractive surgery eyes showed reduced MG expressibility (P=0.021), worse meibum quality (P<0.001), and greater gland loss (P<0.001) than 28 controls.

Our data suggest that MG IL-17 expression increases following corneal nerve injury and may contribute to gland dysfunction. Targeting IL-17 may benefit patients with post-surgical MG dysfunction.