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.

Center for Eye Research Department of Ophthalmology Institute of Clinical Medicine Faculty of Medicine University of Oslo and Oslo University Hospital 0450 Oslo Norway

Department of Cell Biology Faculty of Science Charles University 12808 Prague Czech Republic

Department of Ophthalmology Copenhagen University Hospital Rigshospitalet 2600 Glostrup Denmark

Department of Ophthalmology Justus Liebig University University Hospital Giessen and Marburg GmbH 35392 Giessen Germany

Department of Ophthalmology University Hospital of Split and University of Split 21000 Split Croatia

Eye Translational Research Unit Department of Drug Design and Pharmacology Faculty of Health and Medical Sciences University of Copenhagen 2100 Copenhagen Denmark

Karl Landsteiner Institute for Retinal Research and Imaging 1030 Vienna Austria

Laboratory for Study of Mitochondrial Disorders Department of Paediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University and General University Hospital Prague 12801 Prague Czech Republic

Laboratory of Cell Regeneration and Cell Plasticity Institute of Animal Physiology and Genetics AS CR 277 21 Libechov Czech Republic

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