Macrophage Recruitment in Immune-Privileged Lens During Capsule Repair, Necrotic Fiber Removal and Fibrosis

Summary Emerging evidence challenges the lens as an immune-privileged organ. Here, we provide a direct mechanism supporting a role of macrophages in lens capsule rupture repair. Posterior lens capsule rupture in a connexin 50 and aquaporin 0 double-knockout mouse model resulted in lens tissue extrusion into the vitreous cavity with formation of a “tail-like” tissue containing delayed regressed hyaloid vessels, fibrotic tissue and macrophages at postnatal (P) 15 days. The macrophages declined after P 30 days with M2 macrophages detected inside the lens. By P 90 days, the “tail-like” tissue completely disappeared and the posterior capsule rupture was sealed with thick fibrotic tissue. Colony-stimulating factor 1 (CSF-1) accelerated capsule repair, whereas inhibition of the CSF-1 receptor delayed the repair. Together, these results suggest that lens posterior rupture leads to the recruitment of macrophages delivered by the regression delayed hyaloid vessels. CSF-1-activated M2 macrophages mediate capsule rupture repair and development of fibrosis.
Graphical abstract
Highlights • Lens posterior rupture delays regression of the hyaloid vessels. • Lens posterior rupture recruits macrophages delivered by the hyaloid vessels. • Macrophages mediate necrotic fiber cell removal and capsule rupture sealing. • CSF-1 activated M2 macrophages facilitate capsular rupture sealing by fibrosis.
Immunology; Ophthalmology