Alpha 1-antitrypsin inhibits microglia activation and facilitates the survival of iPSC grafts in hypertension mouse model

Abstract

This study was conducted to investigate the use of Alpha 1-antitrypsin (AAT) to inhibit microglia activation in chronic hypertension model and provide a permissive environment for stem cell transplantation. Chronic ocular hypertension of C57BL/6 mice using magnetic microbead injection was induced 3 weeks prior to iPSCs transplantation. The ocular hypertension model was assessed histologically and intraocular pressure was measured. Survival of grafted cells and microglia activation were examined by flow cytometry and immunofluorescence in AAT and PBS treated hosts. Retinal cytokines expression was also detected by real-time PCR. Chronic ocular hypertension resulted in persistent microglia activation and stem cell grafts loss. AAT treatment significantly inhibited microglia activation and facilitated the survival of transplant iPSCs 4w post transplantation compared to PBS treatment. AAT holds tremendous potential for the clinical application to control neuroinflammation factor in glaucoma and improve the stem cell replacement therapy of retinal neurodegenerative disease.

Keywords: Alpha 1-antitrypsin; Hypertension mouse model; Microglia; Neuroinflammation; iPSC grafts.