Emerging organophosphate flame retardant CDP causes neovascular macular degeneration-like alterations of outer blood-retinal barrier via paracrine VEGFA signaling

  • J Hazard Mater. 2026 Apr 1:507:141669. doi: 10.1016/j.jhazmat.2026.141669.
Yiqun Song  1 ,  Ting Xu  2 ,  Hongchang Zhang  3 ,  Shuangqing Hu  3 ,  Sheng Wei  1 ,  Miao Cao  1 ,  Huan Wang  1 ,  Daqiang Yin  4
Affiliations
  • 1. Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.
  • 2. Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China. Electronic address: [email protected].
  • 3. Shanghai Academy of Environmental Sciences, Shanghai 200233, China.
  • 4. Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China. Electronic address: [email protected].
PMID: 41806579 DOI: 10.1016/j.jhazmat.2026.141669
Abstract

Visual impairment is an urgent public health concern. Increasing epidemiological research has demonstrated a strong correlation between environmental contaminant exposure and retinal diseases, but the underlying mechanism remains unclear. The disruption of the outer blood-retinal barrier (oBRB) is closely implicated in the pathogenesis of multiple vision-threatening disorders. Given its critical physiological role and anatomical position, we systematically investigated the effects of cresyl diphenyl phosphate (CDP, one emerging organophosphate flame retardant) on the oBRB, applying both zebrafish larvae and an in vitro human oBRB model consisting of ARPE-19 and HUVECs. The downregulation of tight junction expression and retinal neovascularization were observed in the zebrafish larvae under CDP treatment. The establishment of the oBRB model further discovered that CDP exposure caused barrier dysfunction and increased VEGFA secretion of ARPE-19. Through the paracrine signaling, VEGFA promoted the angiogenesis of HUVECs, eliciting pathological feature similar to neovascular macular degeneration. This study was the first to reveal an association between eOPFR exposure and retinal-related diseases, highlighting the significance of paracrine signaling in the pathological process.

Keywords
CDP; Neovascular macular degeneration; OBRB; Paracrine VEGFA signaling; eOPFRs.
Products