# From fibrotic mechanisms to clinical translation: the drug therapy revolution and delivery system breakthrough in proliferative vitreoretinopathy

**Authors:** Zijian Chen, Jiangying Liu, Liao Quan, Lingdan Wu, Qihua Xu

PMC · DOI: 10.3389/fimmu.2026.1774802 · Frontiers in Immunology · 2026-02-10

## TL;DR

This paper reviews the complex mechanisms of proliferative vitreoretinopathy and highlights new drug delivery systems as a promising treatment approach.

## Contribution

The paper provides a comprehensive analysis of PVR pathogenesis and evaluates emerging therapeutic strategies, especially drug delivery systems.

## Key findings

- PVR involves RPE cells, glial cells, and inflammatory cells undergoing epithelial-mesenchymal transition.
- Current treatments have high recurrence rates and lack effective adjuvant drugs.
- Innovative drug delivery systems are a key focus for overcoming pharmacological barriers.

## Abstract

Proliferative vitreoretinopathy (PVR) is a severe fibrotic complication following ocular trauma or retinal detachment surgery, characterized by complex multicellular and multicytokine interactions. Its core mechanism involves retinal pigment epithelial (RPE) cells, glial cells, and inflammatory cells undergoing epithelial-mesenchymal transition (EMT), abnormal proliferation, migration, and contraction, ultimately leading to traction retinal detachment. Current treatment primarily relies on surgery, but faces limitations such as high postoperative recurrence rates and a lack of clinically approved effective adjuvant drugs. This review provides a comprehensive analysis of the PVR pathogenic network, integrating the roles of diverse cellular players with key signaling pathways. We place a particular emphasis on critically evaluating emerging therapeutic strategies, including targeted pathway inhibitors and, notably, innovative drug delivery systems, which represent a paradigm shift towards overcoming pharmacological barriers. By synthesizing mechanistic insights with translational applications, this article highlights current advances and underscores the gap between preclinical promise and clinical efficacy. It aims to serve as a timely resource for understanding the pathobiology of PVR and for guiding the development of future multi-targeted therapeutic interventions.

## Linked entities

- **Diseases:** proliferative vitreoretinopathy (MONDO:0100450), retinal detachment (MONDO:0008375)

## Full-text entities

- **Genes:** MAPK3 (mitogen-activated protein kinase 3) [NCBI Gene 5595] {aka ERK-1, ERK1, ERT2, HS44KDAP, HUMKER1A, P44ERK1}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, PDGFRA (platelet derived growth factor receptor alpha) [NCBI Gene 5156] {aka CD140A, PDGFR-2, PDGFR2}, TJP1 (tight junction protein 1) [NCBI Gene 7082] {aka ZO-1}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, NFATC1 (nuclear factor of activated T cells 1) [NCBI Gene 4772] {aka NF-ATC, NF-ATc1.2, NFAT2, NFATc}, CSNK1A1 (casein kinase 1 alpha 1) [NCBI Gene 1452] {aka CK1, CK1a, CKIa, HEL-S-77p, HLCDGP1, PRO2975}, NRTN (neurturin) [NCBI Gene 4902] {aka NTN}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, SNAI1 (snail family transcriptional repressor 1) [NCBI Gene 6615] {aka SLUGH2, SNA, SNAH, SNAIL, SNAIL1, dJ710H13.1}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, MCAM (melanoma cell adhesion molecule) [NCBI Gene 4162] {aka CD146, HEMCAM, METCAM, MUC18, MelCAM}, GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, TGFB2 (transforming growth factor beta 2) [NCBI Gene 7042] {aka CAEND2, G-TSF, LDS4, TGF-beta2}, ELN (elastin) [NCBI Gene 2006] {aka ADCL1, SVAS, WBS, WS}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, RHO (rhodopsin) [NCBI Gene 6010] {aka CSNBAD1, OPN2, RP4}, PDGFRB (platelet derived growth factor receptor beta) [NCBI Gene 5159] {aka CD140B, IBGC4, IMF1, JTK12, KOGS, OPDKD}, THBS1 (thrombospondin 1) [NCBI Gene 7057] {aka THBS, THBS-1, TSP, TSP-1, TSP1}, JAK1 (Janus kinase 1) [NCBI Gene 3716] {aka AIIDE, JAK1A, JAK1B, JTK3}, MRC1 (mannose receptor C-type 1) [NCBI Gene 4360] {aka CD206, CLEC13D, CLEC13DL, MMR, MRC1L1, bA541I19.1}, AXIN1 (axin 1) [NCBI Gene 8312] {aka AXIN, CMDOH, PPP1R49}, AP1S2 (adaptor related protein complex 1 subunit sigma 2) [NCBI Gene 8905] {aka DC22, MRX59, MRXS21, MRXS5, MRXSF, PGS}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, FGF2 (fibroblast growth factor 2) [NCBI Gene 2247] {aka BFGF, FGF-2, FGFB, HBGF-2}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, CDH2 (cadherin 2) [NCBI Gene 1000] {aka ACOGS, ADHD8, ARVD14, CD325, CDHN, CDw325}, TIMP1 (TIMP metallopeptidase inhibitor 1) [NCBI Gene 7076] {aka CLGI, EPA, EPO, HCI, TIMP, TIMP-1}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, PVR [NCBI Gene 100328928], MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, TGFB3 (transforming growth factor beta 3) [NCBI Gene 7043] {aka ARVD, ARVD1, LDS5, RNHF, TGF-beta3}, IL23A (interleukin 23 subunit alpha) [NCBI Gene 51561] {aka IL-23, IL-23A, IL23P19, P19, SGRF}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, ANGPT4 (angiopoietin 4) [NCBI Gene 51378] {aka ANG3, ANG4}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, NTN4 (netrin 4) [NCBI Gene 59277] {aka PRO3091}, GDNF (glial cell derived neurotrophic factor) [NCBI Gene 2668] {aka ATF, ATF1, ATF2, HFB1-GDNF, HSCR3}, RUNX1 (RUNX family transcription factor 1) [NCBI Gene 861] {aka AML1, AML1-EVI-1, AMLCR1, CBF2alpha, CBFA2, EVI-1}, CD34 (CD34 molecule) [NCBI Gene 947], CCN2 (cellular communication network factor 2) [NCBI Gene 1490] {aka CTGF, HCS24, IBP-8, IGFBP8, KMD, NOV2}, DKK1 (dickkopf Wnt signaling pathway inhibitor 1) [NCBI Gene 22943] {aka DKK-1, SK}, HNF4A (hepatocyte nuclear factor 4 alpha) [NCBI Gene 3172] {aka FRTS4, HNF4, HNF4a7, HNF4a8, HNF4a9, HNF4alpha}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, EDN1 (endothelin 1) [NCBI Gene 1906] {aka ARCND3, ET1, HDLCQ7, PPET1, QME}, FAP (fibroblast activation protein alpha) [NCBI Gene 2191] {aka DPPIV, FAPA, FAPalpha, SIMP}, WNT1 (Wnt family member 1) [NCBI Gene 7471] {aka BMND16, INT1, OI15}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, ACTA1 (actin alpha 1, skeletal muscle) [NCBI Gene 58] {aka ACTA, ASMA, CFTD, CFTD1, CFTDM, CMYO2A}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, ARG1 (arginase 1) [NCBI Gene 383], IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}
- **Diseases:** eye disease (MESH:D005128), retinal diseases (MESH:D012164), RRD (MESH:C563710), toxicity (MESH:D064420), proliferative retinopathy (OMIM:603933), cystoid macular edema (MESH:D008269), retinal fibrosis (MESH:D012173), retinal tears (MESH:D012167), hypoxia (MESH:D000860), RD (MESH:D012163), ocular toxicity (MESH:D000081028), hypoxic (MESH:D002534), PVR (MESH:D018630), avascular (MESH:D010020), OGI (MESH:D006259), ocular trauma (MESH:D014947), inflammation (MESH:D007249), fibrosis (MESH:D005355)
- **Chemicals:** LMWH (MESH:D006495), TA (MESH:D014222), ROS (MESH:D017382), PLGA (MESH:D000077182), heparin (MESH:D006493), lipid (MESH:D008055), polyepsilon-caprolactone (MESH:C016240), dexamethasone (MESH:D003907), PMEG (MESH:C063380), dasatinib (MESH:D000069439), PVA (MESH:D011142), GAGs (MESH:D006025), retinoic acid (MESH:D014212), silica (MESH:D012822), doxorubicin (MESH:D004317), Poly(L-lactide)-co-poly(epsilon-caprolactone) (-), neferine (MESH:C057222), bevacizumab (MESH:D000068258), artesunate (MESH:D000077332), infliximab (MESH:D000069285), hyaluronic acid (MESH:D006820), demethoxycurcumin (MESH:C050229), daunorubicin (MESH:D003630), 5-FU (MESH:D005472), curcuminoid (MESH:D036381), methotrexate (MESH:D008727), carotenoid (MESH:D002338), PEG-b-PCL (MESH:C521904), crocetin (MESH:C487773), chitosan (MESH:D048271), sodium alginate (MESH:D000464), doxycycline (MESH:D004318), succinic acid (MESH:D019802)
- **Species:** Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** RPE — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0145)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12929120/full.md

## References

137 references — full list in the complete paper: https://tomesphere.com/paper/PMC12929120/full.md

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Source: https://tomesphere.com/paper/PMC12929120