June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
PEGlyated TRAIL alleviats alkali burn induced rat corneal fibrosis by targeting DR5
Author Affiliations & Notes
  • Minjie Chen
    Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Hui Lin
    Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Stefanie Seo
    Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Yumin Oh
    D&D Pharmatech, Gaithersburg, Maryland, United States
  • Seulki Lee
    Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
    D&D Pharmatech, Gaithersburg, Maryland, United States
  • Samuel C Yiu
    Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Minjie Chen, None; Hui Lin, None; Stefanie Seo, None; Yumin Oh, D&D Pharmatech (E); Seulki Lee, D&D Pharmatech (E); Samuel Yiu, D&D Pharmatech (F)
  • Footnotes
    Support  D&D TRAIL study
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 748. doi:
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    • Get Citation

      Minjie Chen, Hui Lin, Stefanie Seo, Yumin Oh, Seulki Lee, Samuel C Yiu; PEGlyated TRAIL alleviats alkali burn induced rat corneal fibrosis by targeting DR5. Invest. Ophthalmol. Vis. Sci. 2021;62(8):748.

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

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Abstract

Purpose : Corneal fibrosis and neovascularization are inevitable outcome of corneal alkali burn injury. Here we determine whether TLY012, a PEGylated TNF-related apoptosis-inducing ligand (TRAILpeg) could provide preventive effects against corneal fibrosis through death recepter 5 (DR5) dependent pathway in a murine alkali burn model.

Methods : To induced corneal fibrosis, ten (10) Sprague-Dawley rats (age 6-8 weeks, male) were treated by applying 0.5N NaOH to the cornea for 90 seconds. After 7 days, rats were randomly assigned into treatment (TLY012, 10 mg/mL, 50uL subconj) or control (PBS 50ul subconj) groups and treated twice a week for the following 14 days. Corneal opacity, neovascularization, edema, and flare were recorded. Analysis of DR5 and α-smooth muscle actin (α-SMA) immunofluorescent staining of rat cornea were performed after rat euthanizing at 21 days.

Results : TLY012 significantly decreased corneal opacity score (0.9 ± 0.19 vs 1.9 ± 0.33, *p≤0.05) and neovascularization score (1.0 ± 0.22 vs 2.4 ± 0.33, **p≤0.01) compared to PBS group in alkali burn injured rat cornea at D21 . TLY012 facilitated corneal flare clearness and transiently slowed corneal edema recovery, but there was no detectable difference between two groups at D21. DR5 were present in corneal epithelium and stroma in PBS treatment group at D21, and its expression was attenuated with TLY012 treatment. Correspondingly, α-SMA staining were noticeably reduced in epithelium and stroma layer with TLY012 treatment. Additionally, TLY012 decreased blood vessel density in corneal stroma induced by alkali injury.

Conclusions : Our experiment showed that TLY012 prevents corneal neovascularization and fibrosis induced by ocular alkali burn injury. These results demostrated that TLY012 could be a novel candidate for treating corneal fibrotic disease.

This is a 2021 ARVO Annual Meeting abstract.

 

Fig1: Corneal opacity, neovascularization, edema and flare score in TLY012 or PBS treated alkali burn rat cornea

Fig1: Corneal opacity, neovascularization, edema and flare score in TLY012 or PBS treated alkali burn rat cornea

 

DR5 and α-SMA staining in TLY012 or PBS treated alkali burn rat cornea at D21. Blue arrow: DR5; yellow arrow: α -SMA in the epithelium; green arrow: α -SMA in the stroma; white arrow: α -SMA indicating blood vessel.

DR5 and α-SMA staining in TLY012 or PBS treated alkali burn rat cornea at D21. Blue arrow: DR5; yellow arrow: α -SMA in the epithelium; green arrow: α -SMA in the stroma; white arrow: α -SMA indicating blood vessel.

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