Mitochondrial Dysfunction in a High Intraocular Pressure-Induced Retinal Ischemia Minipig Model

Michael Pasák, Marie Vanišová, Lucie Tichotová, Jana Křížová, Taras Ardan, Yaroslav Nemesh, Jana Čížková, Anastasiia Kolesnikova, Ruslan Nyshchuk, Natasha Josifovska, Lyubomyr Lytvynchuk, Miriam Kolko, Jan Motlík, Goran Petrovski*, Hana Hansíková*

*Corresponding author for this work

Abstract

Purpose: Retinal ischemia (RI) and progressive neuronal death are sight-threatening conditions. Mitochondrial (mt) dysfunction and fusion/fission processes have been suggested to play a role in the pathophysiology of RI. This study focuses on changes in the mt parameters of the neuroretina, retinal pigment epithelium (RPE) and choroid in a porcine high intraocular pressure (IOP)-induced RI minipig model. Methods: In one eye, an acute IOP elevation was induced in minipigs and compared to the other control eye. Activity and amount of respiratory chain complexes (RCC) were analyzed by spectrophotometry and Western blot, respectively. The coenzyme Q10 (CoQ10) content was measured using HPLC, and the ultrastructure of the mt was studied via transmission electron microscopy. The expression of selected mt-pathway genes was determined by RT-PCR. Results: At a functional level, increased RCC I activity and decreased total CoQ10 content were found in RPE cells. At a protein level, CORE2, a subunit of RCC III, and DRP1, was significantly decreased in the neuroretina. Drp1 and Opa1, protein-encoding genes responsible for mt quality control, were decreased in most of the samples from the RPE and neuroretina. Conclusions: The eyes of the minipig can be considered a potential RI model to study mt dysfunction in this disease. Strategies targeting mt protection may provide a promising way to delay the acute damage and onset of RI.

Original languageEnglish
Article number1532
JournalBiomolecules
Volume12
Issue number10
ISSN2218-273X
DOIs
Publication statusPublished - 21 Oct 2022

Keywords

  • Animals
  • Swine
  • Intraocular Pressure
  • Swine, Miniature
  • Carcinoma, Renal Cell/metabolism
  • Glaucoma/metabolism
  • Kidney Neoplasms/metabolism
  • Mitochondria/metabolism
  • Ischemia/metabolism

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