Dataset Information

P21CIP/WAF1 saRNA inhibits proliferative vitreoretinopathy in a rabbit model.

ABSTRACT:

Purpose

Proliferative vitreoretinopathy (PVR) is a disease process resulting from proliferation of retinal pigment epithelial (RPE) cells in the vitreous and periretinal area, leading to periretinal membrane formation and traction and eventually to postoperative failure after vitreo-retinal surgery for primary rhegmatogenous retinal detachment (RRD). The present study was designed to test the therapeutic potential of a p21CIP/WAF1 (p21) inducing saRNA for PVR.

Methods

A chemically modified p21 saRNA (RAG1-40-53) was tested in cultured human RPE cells for p21 induction and for the inhibition of cell proliferation, migration and cell cycle progression. RAG1-40-53 was further conjugated to a cholesterol moiety and tested for pharmacokinetics and pharmacodynamics in rabbit eyes and for therapeutic effects after intravitreal administration in a rabbit PVR model established by injecting human RPE cells.

Results

RAG1-40-53 (0.3 mg, 1 mg) significantly induced p21 expression in RPE cells and inhibited cell proliferation, the progression of cell cycle at the G0/G1 phase and TGF-β1 induced migration. After a single intravitreal injection into rabbit eyes, cholesterol-conjugated RAG1-40-53 exhibited sustained concentration in the vitreal humor beyond at least 8 days and prevented the progression of established PVR.

Conclusion

p21 saRNA could represent a novel therapeutics for PVR by exerting a antiproliferation and antimigration effect on RPE cells.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC9949646 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

p21CIP/WAF1 saRNA inhibits proliferative vitreoretinopathy in a rabbit model.

Zhang Qi Q Guo Yangchen Y Kang Moorim M Lin Wei-Hsiang WH Wu Jian-Cheng JC Yu Ying Y Li Long-Cheng LC Sang Aimin A

PloS one 20230223 2

<h4>Purpose</h4>Proliferative vitreoretinopathy (PVR) is a disease process resulting from proliferation of retinal pigment epithelial (RPE) cells in the vitreous and periretinal area, leading to periretinal membrane formation and traction and eventually to postoperative failure after vitreo-retinal surgery for primary rhegmatogenous retinal detachment (RRD). The present study was designed to test the therapeutic potential of a p21CIP/WAF1 (p21) inducing saRNA for PVR.<h4>Methods</h4>A chemically ...[more]

PMID: 36821623

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