LIF, a mitogen for choroidal endothelial cells, protects the choriocapillaris: implications for prevention of geographic atrophy.

Pin Li, Qin Li, Nilima Biswas, Hong Xin, Tanja Diemer, Lixian Liu, Lorena Perez Gutierrez, Giovanni Paternostro, Carlo Piermarocchi, Sergii Domanskyi, Ruikang K Wang, Napoleone Ferrara

EMBO molecular medicine 2022 Jan 11

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In the course of our studies aiming to discover vascular bed-specific endothelial cell (EC) mitogens, we identified leukemia inhibitory factor (LIF) as a mitogen for bovine choroidal EC (BCE), although LIF has been mainly characterized as an EC growth inhibitor and an anti-angiogenic molecule. LIF stimulated growth of BCE while it inhibited, as previously reported, bovine aortic EC (BAE) growth. The JAK-STAT3 pathway mediated LIF actions in both BCE and BAE cells, but a caspase-independent proapoptotic signal mediated by cathepsins was triggered in BAE but not in BCE. LIF administration directly promoted activation of STAT3 and increased blood vessel density in mouse eyes. LIF also had protective effects on the choriocapillaris in a model of oxidative retinal injury. Analysis of available single-cell transcriptomic datasets shows strong expression of the specific LIF receptor in mouse and human choroidal EC. Our data suggest that LIF administration may be an innovative approach to prevent atrophy associated with AMD, through protection of the choriocapillaris. © 2021 The Authors. Published under the terms of the CC BY 4.0 license.

Citation

Pin Li, Qin Li, Nilima Biswas, Hong Xin, Tanja Diemer, Lixian Liu, Lorena Perez Gutierrez, Giovanni Paternostro, Carlo Piermarocchi, Sergii Domanskyi, Ruikang K Wang, Napoleone Ferrara. LIF, a mitogen for choroidal endothelial cells, protects the choriocapillaris: implications for prevention of geographic atrophy. EMBO molecular medicine. 2022 Jan 11;14(1):e14511