June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Decorin for choroidal neovascularization fibrosis and epithelial-mesenchymal transition of retinal pigment epithelium
Author Affiliations & Notes
  • Francine F Behar-Cohen
    physiopathology of ocular diseases : therpaueitc innovations, Centre de Recherche des Cordeliers, Paris, Île-de-France, France
    OPhthalmopole, Assistance publique-hôpitaux de Paris, Paris, France
  • laura Benichou
    physiopathology of ocular diseases : therpaueitc innovations, Centre de Recherche des Cordeliers, Paris, Île-de-France, France
  • Louis Debillon
    OPhthalmopole, Assistance publique-hôpitaux de Paris, Paris, France
  • Karine Bigot
    Eyevensys, Paris, France
  • Thierry Bordet
    Eyevensys, Paris, France
  • Min Zhao
    physiopathology of ocular diseases : therpaueitc innovations, Centre de Recherche des Cordeliers, Paris, Île-de-France, France
  • Footnotes
    Commercial Relationships   Francine Behar-Cohen Inserm-université de Paris, Code P (Patent); laura Benichou None; Louis Debillon None; Karine Bigot Eyevensys, Code E (Employment); Thierry Bordet Eyevensys, Code E (Employment); Min Zhao Inserm, Université de Paris, Code P (Patent)
  • Footnotes
    Support  UNADEV ITMO MR-A-MD, ANR Grant20-CE17-0034, Eyevensys scientific collaboration
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 3874. doi:
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    • Get Citation

      Francine F Behar-Cohen, laura Benichou, Louis Debillon, Karine Bigot, Thierry Bordet, Min Zhao; Decorin for choroidal neovascularization fibrosis and epithelial-mesenchymal transition of retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 2022;63(7):3874.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Despite anti-VEGF, subretinal fibrosis and scar cause vision loss in wet AMD patients. Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells contributes to subretinal fibrosis. Decorin (DCN) is a proteoglycan with anti-fibrotic and anti-angiogenic properties. The aim of this study was to evaluate the effect of DCN on CNV fibrosis and EMT in a rat model of choroidal neovascularization (CNV)

Methods : Long-Evans rats with to laser-induced CNV were followed by fluorescein angiography (FA) on day 14 and 30. DCN (10µg/eye) or vehicle was injected in the vitreous, either at the time of laser burn, or at day 14, when CNV had developed. At day 30, rats were injected with intravenous FITC-dextran before sacrifice and RPE/ choroid flat-mounts were stained with collagen 1 and phalloidin. CNV volumes were quantified, morphometrics of RPE surrounding laser burns were quantified (size, shape, number of neighbors). In a separate experiment, rats with CNV were injected with DCN at 13 and they were sacrificed at day 16 for RNA seq analysis of RPE-choroid using Illumina HiSeq2000. Differential expression was analyzed using EASYGO threshold-free gene ontology.

Results : On FA, although leakge regressed similarly in both groups at day 30 (71% vs 65% of grade 0 lesions), the CNV volume was significantly reduced in rats treated with DCN at day 14 (p<0.0001). In addition to perivascular collagen 1 staining, a dense plug at the center of the impact could be seen. Day 14 DCN treatment significantly reduced perivascular collagen 1 (p<0.001) and limited the formation of collagen 1-positive scar at the center of the laser burns (31% of the lesions with central scar vs 62% in controls).
In control rats, at day 30, the RPE that surround the laser burn undergo EMT, with significant increase in RPE mean area and elongation. While no effect of DCN at day 14 was seen on EMT at day 30, normalization of RPE morphometrics was observed with DCN administration at the time of laser. RNA seq analysis showed that DCN significantly regulated pathway involved in angiogenesis, fibrosis, EMT, oxidative stress, inflammation and nerve maturation

Conclusions : DCN reduces the volume of established CNV and its fibrotic scaring. Early DCN treatment prevents EMT.
DCN is a promising candidate for wet AMD patients on top of anti-VEGFs therapies

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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