TSPAN4-positive migrasome derived from retinal pigmented epithelium cells contributes to the development of

Liangjing Wu1, Shuai Yang1, Hui Li1

  • 1Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.

Abstract

Insights

Migrosomes, vesicles linked to cell migration, promote retinal pigmented epithelium (RPE) activation and proliferative vitreoretinopathy (PVR) progression. Targeting TSPAN4 or blocking migrasome formation offers a potential new therapy for PVR.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Extracellular Vesicles

Background:

  • Proliferative vitreoretinopathy (PVR) is a major cause of blindness.
  • Retinal pigmented epithelium (RPE) activation, often induced by TGF-β, initiates PVR.
  • Migrosomes are newly identified extracellular vesicles involved in cell migration.

Purpose of the Study:

  • To investigate the role and characteristics of migrosomes in RPE activation and PVR development.
  • To explore the potential of targeting migrosomes for PVR therapy.

Main Methods:

  • Utilized ex vivo, in vitro, and in vivo models.
  • Analyzed human PVR clinical samples for migrosome marker TSPAN4 expression.
  • Employed electron microscopy to visualize migrosome formation.
  • Investigated the TGF-β1/Smad2/3 signaling pathway's role in migrosome production.

Main Results:

  • TSPAN4, a migrosome marker, was highly expressed in human PVR samples.
  • TGF-β1 stimulation induced RPE activation, TSPAN4 expression, and migrosome production.
  • Internalization of migrosomes enhanced RPE migration and proliferation.
  • Inhibition of TSPAN4 reduced RPE's ability to initiate experimental PVR.

Conclusions:

  • Migrosomes are produced by RPE in a PVR microenvironment.
  • Migrosomes play a significant role in RPE activation and PVR progression.
  • Targeting TSPAN4 or inhibiting migrosome formation presents a novel therapeutic strategy for PVR.

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