June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Involvement of thioredoxin system in laser induced CNV mouse model
Author Affiliations & Notes
  • Robertas Cesna
    Research & Development Division, Experimentica Ltd., Vilnius, Lithuania
    State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
  • Dovile Litvinaviciute
    Research & Development Division, Experimentica Ltd., Vilnius, Lithuania
  • Justina Urbanaviciute
    Research & Development Division, Experimentica Ltd., Vilnius, Lithuania
  • Inesa Lelyte
    Research & Development Division, Experimentica Ltd., Vilnius, Lithuania
  • Kernius Mickevicius
    Research & Development Division, Experimentica Ltd., Vilnius, Lithuania
  • Odeta Adamoniene
    Research & Development Division, Experimentica Ltd., Vilnius, Lithuania
  • Donatas Neverauskas
    Research & Development Division, Experimentica Ltd., Vilnius, Lithuania
    State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
  • Symantas Ragauskas
    Research & Development Division, Experimentica Ltd., Vilnius, Lithuania
  • Giedrius Kalesnykas
    Research & Development Division, Experimentica Ltd., Vilnius, Lithuania
  • Anita K. Ghosh
    Research and Development Division, Experimentica Ltd, Illinois, United States
  • Simon Kaja
    Research and Development Division, Experimentica Ltd, Illinois, United States
    Ophthalmology and Molecular Pharmacology & Neuroscience, Loyola University Chicago, Maywood, Illinois, United States
  • Footnotes
    Commercial Relationships   Robertas Cesna None; Dovile Litvinaviciute None; Justina Urbanaviciute None; Inesa Lelyte None; Kernius Mickevicius None; Odeta Adamoniene None; Donatas Neverauskas None; Symantas Ragauskas None; Giedrius Kalesnykas None; Anita Ghosh None; Simon Kaja None
  • Footnotes
    Support  Experimentica Ltd.; Dr. John P. and Therese E. Mulcahy Endowed Professorship in Ophthalmology
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2727. doi:
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      Robertas Cesna, Dovile Litvinaviciute, Justina Urbanaviciute, Inesa Lelyte, Kernius Mickevicius, Odeta Adamoniene, Donatas Neverauskas, Symantas Ragauskas, Giedrius Kalesnykas, Anita K. Ghosh, Simon Kaja; Involvement of thioredoxin system in laser induced CNV mouse model. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2727.

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

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Abstract

Purpose : Thioredoxin-interacting protein (TXNIP) plays important role in cellular redox-state homeostasis by binding and inhibiting thioredoxin. Cellular redox homeostasis controlled by thioredoxin regulates vascular endothelial growth factor (VEGF) expression. The objective of this Study was to evaluate expression of key genes of the thioredoxin-VEGF pathway (thioredoxin-1, TXN1; TXNIP; hypoxia-inducible factor 1-alpha (HIF1A; vascular endothelial growth factor A, VEGFA) in the in mouse laser-induced choroidal neovascularization (CNV) model.

Methods : CNV was induced unilaterally in in 8-week-old male C57BL/6JRj mice (n=20) by penetrating Bruch’s membrane with a diode laser on Day 0. An additional 4 mice served as naïve control group without CNV induction. Pathology was monitored by in vivo imaging using fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT) on Day 0, 1, 3, 7 and 10 post-CNV. CNV animals were randomized into 4 experimental groups sacrificed at Day 1, 3, 7 or 10. Retinas were collected, snap frozen with liquid nitrogen. Total RNA was extracted using chloroform/TRIzol mixture and cDNA synthesis was performed using High-Capacity RNA-to-cDNA Kit (Thermo Fisher). Validated Taqman® Gene Expression assays (Thermo Fisher) were used for the qPCR reaction. GAPDH were used as endogenous control. Data were analyzed using the 2-△△CT method for relative quantification and graphed and statistically tested using Prism software (Graphpad, Inc.).

Results : TXN1 (p<0.05) and TXNIP (p<0.05) gene expression were significantly increased (~ 2-fold) in CNV eyes on Day 1 post-CNV when compared to naïve eyes. The increase in TXN1 expression was sustained through Day 3 (p<0.05). In contrast, HIF1A and VEGFA gene expression were decreased by ~25% on Day 7.

Conclusions : Our data support involvement of the thioredoxin system in regulating VEGF expression system in CNV pathophysiology in mice. Targeting the thioredoxin system early during CNV pathology may offer therapeutic opportunities of attenuating progression of CNV pathology in mice.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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