Mitochondrial Dysfunction in a High Intraocular Pressure-Induced Retinal Ischemia Minipig Model
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Mitochondrial Dysfunction in a High Intraocular Pressure-Induced Retinal Ischemia Minipig Model. / Pasák, Michael; Vanišová, Marie; Tichotová, Lucie; Křížová, Jana; Ardan, Taras; Nemesh, Yaroslav; Čížková, Jana; Kolesnikova, Anastasiia; Nyshchuk, Ruslan; Josifovska, Natasha; Lytvynchuk, Lyubomyr; Kolko, Miriam; Motlík, Jan; Petrovski, Goran; Hansíková, Hana.
In: Biomolecules, Vol. 12, No. 10, 1532, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Mitochondrial Dysfunction in a High Intraocular Pressure-Induced Retinal Ischemia Minipig Model
AU - Pasák, Michael
AU - Vanišová, Marie
AU - Tichotová, Lucie
AU - Křížová, Jana
AU - Ardan, Taras
AU - Nemesh, Yaroslav
AU - Čížková, Jana
AU - Kolesnikova, Anastasiia
AU - Nyshchuk, Ruslan
AU - Josifovska, Natasha
AU - Lytvynchuk, Lyubomyr
AU - Kolko, Miriam
AU - Motlík, Jan
AU - Petrovski, Goran
AU - Hansíková, Hana
N1 - Funding Information: This project was supported by IP-20 No.41 by General University Hospital in Prague, MZ CR RVO-VFN64165. The study was in part supported by the international project of The Czech Science Foundation (Project Number 18-04393S) and Technology Agency of the Czech Republic (KAPPA project TO01000107). Publisher Copyright: © 2022 by the authors.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - coenzyme Q10
KW - minipig
KW - mitochondrial dysfunction
KW - retinal ischemia
U2 - 10.3390/biom12101532
DO - 10.3390/biom12101532
M3 - Journal article
C2 - 36291741
AN - SCOPUS:85140449851
VL - 12
JO - Biomolecules
JF - Biomolecules
SN - 2218-273X
IS - 10
M1 - 1532
ER -
ID: 327065369