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

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

  • EMBO Mol Med. 2022 Jan 11;14(1):e14511. doi: 10.15252/emmm.202114511.
Pin Li 1 Qin Li 2 Nilima Biswas 1 Hong Xin 1 Tanja Diemer 1 Lixian Liu 1 Lorena Perez Gutierrez 1 Giovanni Paternostro 3 Carlo Piermarocchi 4 Sergii Domanskyi 4 Ruikang K Wang 5 Napoleone Ferrara 1 2
Affiliations

Affiliations

  • 1 Department of Pathology, University of California San Diego, La Jolla, CA, USA.
  • 2 Department of Ophthalmology, University of California San Diego, La Jolla, CA, USA.
  • 3 Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
  • 4 Department of Physics and Astronomy, Michigan State University, East Lansing, MI, USA.
  • 5 Department of Bioengineering, University of Washington, Seattle, WA, USA.
Abstract

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.

Keywords

IL-6 family; STAT3; age-related macular degeneration; cathepsins; endothelial diversity.

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