Lilrb2-mediated inhibition of scleral remodeling in experimental myopia is associated with reduced intraocular inflammation and modulation of the MEK-ERK-P65 axis.

Abstract

OBJECTIVE: This study aimed to investigate the role of leukocyte immunoglobulin-like receptor B2 (Lilrb2) in suppressing scleral remodeling in a guinea pig model of lens-induced myopia (LIM), with a focus on its ability to modulate the intraocular inflammatory microenvironment. METHODS: An LIM model was established in guinea pigs using -6.0 D lenses. Animals received an intravitreal injection of an adeno-associated virus overexpressing Lilrb2 (AAV-Lilrb2). Ocular biometric parameters were monitored. The activity of the MEK-ERK-P65 signaling pathway in the retina and the protein levels of MMP-2, collagen I, and α-SMA in the sclera were assessed using qPCR and Western blot. Macrophage polarization states were evaluated via multiplex immunofluorescence and Western blot analysis of iNOS (M1 marker) and ARG1 (M2 marker). Structural changes in the sclera were examined by H&E staining, while collagen organization and fibrosis were evaluated using Masson staining and immunofluorescence. RESULTS: Compared with the normal control (NC) group, the LIM group exhibited significant axial elongation and a myopic shift in refractive error. In the retina, LIM promoted M1 macrophage polarization, activated the MEK-ERK-P65 pathway, and elevated pro-inflammatory cytokine levels. In the sclera, M2 macrophage polarization was enhanced and accompanied by increased MMP-2 expression and reduced levels of α-SMA and collagen I. Histological analysis revealed disorganized collagen fibers and widened interfibrillar spaces in the LIM sclera, indicative of active scleral remodeling. These changes were effectively counteracted by Lilrb2 overexpression, which attenuated intraocular inflammation and suppressed scleral remodeling. CONCLUSION: Lilrb2 overexpression mitigates myopia progression by ameliorating intraocular inflammation and inhibiting scleral remodeling in a guinea pig model of LIM, highlighting its potential as a therapeutic target for myopia control.