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Updated: Aug 18, 2025

Retinal Pigment Epithelium Transplantation in a Non-human Primate Model for Degenerative Retinal Diseases
Published on: June 14, 2021
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.
Background:
Proliferative vitreoretinopathy (PVR) is a blind-causing disease initiated by the activation of retinal pigmented epithelium (RPE) primarily induced by TGF-β families. Migrasome is a recently discovered type of extracellular vesicle related to cell migration.
Results:
Here, we used ex vivo, in vitro, and in vivo models, to investigate the characteristics and functions of migrasomes in RPE activation and PVR development. Results indicated that the migrasome marker tetraspanin-4 (TSPAN4) was abundantly expressed in human PVR-associated clinical samples. The ex vivo model PVR microenvironment is simulated by incubating brown Norway rat RPE eyecups with TGF-β1. Electron microscope images showed the formation of migrasome-like vesicles during the activation of RPE. Further studies indicated TGF-β1 increased the expression of TSPAN4 which results in migrasome production. Migrasomes can be internalized by RPE and increase the migration and proliferation ability of RPE. Moreover, TSPAN4-inhibited RPE cells are with reduced ability of initiating experimental PVR. Mechanically, TSPAN4 expression and migrasome production are induced through TGF-β1/Smad2/3 signaling pathway.
Conclusion:
In conclusion, migrasomes can be produced by RPE under PVR microenvironment. Migrasomes play a pivotal role in RPE activation and PVR progression. Thus, targeting TSPAN4 or blocking migrasome formation might be a new therapeutic method against PVR.
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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