Chalcomoracin prevents vitreous-induced activation of AKT and migration of retinal pigment epithelial cells

  • J Cell Mol Med. 2021 Oct;25(19):9102-9111. doi: 10.1111/jcmm.16590.
Haote Han  1  2  3  4 Yanhui Yang  5 Bing Liu  6 Jingkui Tian  1  2 Lijun Dong  7 Hui Qi  7 Wei Zhu  1  2 Jiantao Wang  7 Hetian Lei  7
Affiliations
  • 1. Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Zhejiang Cancer Hospital, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China.
  • 2. College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China.
  • 3. Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USA.
  • 4. Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
  • 5. School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
  • 6. Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • 7. Shenzhen Eye Hospital, Shenzhen Eye Institute, Jinan University, Shenzhen, China.
Abstract

Retinal pigment epithelial (RPE) cells are the major cell type in the epi- or sub-retinal membranes in the pathogenesis of proliferative vitreoretinopathy (PVR), which is a blinding fibrotic eye disease and still short of effective medicine. The purpose of this study is to demonstrate whether Chalocomoracin (CMR), a novel purified compound from fungus-infected mulberry leaves, is able to inhibit vitreous-induced signalling events and cellular responses intrinsic to PVR. Our studies have revealed that the CMR IC50 for ARPE-19 cells is 35.5 μmol/L at 72 hours, and that 5 μmol/L CMR inhibits vitreous-induced Akt activation and p53 suppression; in addition, we have discovered that this chemical effectively blocks vitreous-stimulated proliferation, migration and contraction of ARPE-19 cells, suggesting that CMR is a promising PVR prophylactic.

Keywords
Akt; chalocomoracin; contraction; migration; p53; proliferation; proliferative vitreoretinopathy; vitreous.