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Yuting Li, Sumin Gu, Hongyun Cheng, Jean X Jiang; Macrophages Play a Key Role in Repairing Lens Posterior Capsule Rapture, Fiber Protrusion and Promotion of Fibrosis. Invest. Ophthalmol. Vis. Sci. 2020;61(7):5024.
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© ARVO (1962-2015); The Authors (2016-present)
With increasing evidence of the immune process in the lens, the concept of lens as an immune privileged organ has been recently challenged. However, how the immune responses are evoked and functional in the lens remains elusive. In this study, we provided direct evidence supporting the role of macrophages in the rupture repair of posterior lens capsule and fibrosis.
A double knockout (dKO) mouse model deficient in connexin (Cx) 50 and Aquaporin 0 (AQP0) was generated and dKO mice exhibits a phenotype of posterior lens capsule rupture. We used light microscopy, histochemical analysis, immuno-labeling and TUNEL assay to determine macrophages, hyaloid vessels, epithelial mesenchymal transition (EMT), fibrosis and apoptosis at various developmental stages of lenses from WT and dKO mice.
Our previous studies show that dKO mice exhibit small eyes and lens with severe cataracts and morphological defects including posterior capsule rupture. We found here that lens fiber tissues were subsequently extruded from ruptured posterior capsule to the vitreous body at postnatal age of 15 days (P15) (95.24%, n=21). By histochemical analysis, we observed a tail-like tissue consisting of disorganized lens fiber cells, hyaloid vessels, fibrotic tissue and macrophages. The delayed regression of the hyaloid vessel system and increased fibrosis were detected with anti-SMA after P15. Immunofluorescence with anti-CD68 and anti-Cx46 antibodies showed the presence of Cx46-positive cells inside the macrophages, suggesting the phagocytic process of macrophages. Co-labeling with anti-CD68 and anti-caspase-3 antibodies or TUNEL staining, we observed that apoptotic fiber cells were surrounded by macrophages in tail-like tissue at P15. Macrophages continued migrating towards the interior part of the lens after P30, coinciding with an increase in apoptotic fiber cells. By P90, the lens fiber protrusion disappeared and posterior capsule rupture was healed (89.47%, n=19). Moreover, fibrosis increased at P15 and with aggravation of fibrosis, capsule thickness increased and the epithelial cells imitated EMT process after P30.
The results suggest that posterior rupture of lens and apoptosis lead to the recruitment of macrophages delivered by delayed regression of hyaloid vessel system. Macrophages help repair the capsule rapture and fiber protrusion via phagocytosis and fibrosis/EMT.
This is a 2020 ARVO Annual Meeting abstract.
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