Lv_2026_Exp.Eye.Res_270_111137

Angiotensin-converting enzyme inhibitor (ACEI) imidapril potentially affects the CD26/dipeptidyl peptidase IV (DDP IV) system to alleviate laser induced murine choroidal neovascularization (CNV) lesions, but the underlying mechanism is not well understood. The present study aimed to investigate the role of CD26 in promoting bone marrow-derived cell (BMC) mobilization and differentiation in the CNV area to repair laser induced injury. Hereby, adult wild mice were engrafted with total BMCs extracted from GFP transgenic mice and were subjected to laser-induced CNV in turn. And CD26/DDP IV activator (imidapril) and inhibitor (diprotin-A, Dip-A) were separately or together prescribed 5 days prior to and 14 days after CNV modeling. Accordingly, we found that imidapril failed to change CD26(+) cell counts despite significantly increased CD26 enzymatic activity in bone marrow (BM). However, imidapril substantially suppressed CD26(+) cell ratio and activity in peripheral blood (PB). Dip-A treatment alone failed to affect CD26(+) cell count despite suppressed CD26 activity. Imidapril effectively reduced CNV length, thickness, and volume as well as retina-choroidal permeability, while Dip-A did not affect CNV severity. Moreover, imidapril but not Dip-A treatment increased BMC fractions in PB and CNV. When CNV mice were treated with imidapril, SDF-1 in PB was significantly increased at day 3 and peaked at day 7. In contrast, SDF-1 in BM was substantially reduced at day 3 and profoundly reduced at days 7 and 14. The number of retinal pigment epithelial cells, macrophages and microglia derived from mobilized BMCs significantly increased in CNV areas in response to imidapril treatment. These findings indicate that imidapril influences the CD26/SDF-1 axis to promote BMC mobilization and differentiation in a mouse model of CNV, providing a mechanistic basis for further preclinical and translational investigations.