Abstract
Purpose :
Oxidative stress is defined as the overproduction of reactive oxygen species. This pathomechanism occurs in several retinal diseases, including retinal ischemia or glaucoma. Hydrogen peroxide (H2O2) can be used in vitro to simulate oxidative stress, causing a strong neurodegeneration of the inner retinal layers. In this study, we evaluated the potential protective ability of the antioxidant biomolecule coenzyme Q10 (CoQ10) against retinal degeneration processes in a porcine organ culture model.
Methods :
Oxidative damage was induced in porcine retinal organotypic cultures by adding 500 µM H2O2 on day one for three hours. Simultaneously, CoQ10 therapy (700 µM; Life Science) was applied for 48 hours. Retinal ganglion cells (RGCs) and microglia were evaluated via immunohistology and RT-qPCR after eight days. Moreover, cellular, apoptotic, oxidative, and inflammatory genes were quantified via RT-qPCR analyses. Then the following groups were compared: controls, H2O2, and H2O2+CoQ10.
Results :
The H2O2 group had significantly fewer RGCs than controls (p<0.001). CoQ10 protected RGCs compared to the H2O2 group (immunohistology: p<0.001; RT-qPCR: p=0.003). A significant increase in microglial number was detected in the H2O2 group (p=0.004), which was inhibited by CoQ10 (p=0.26). A significantly increased expression of the apoptotic marker BAX/BCL2 was observed in the H2O2 group (1.56-fold; p=0.02), which could be prevented by CoQ10 treatment (0.99-fold; p=0.93). Cellular protection cascades against oxidative stress, NRF2 (2.86-fold; p=0.01) and HMOX1 transcriptional machinery (1.43-fold; p=0.05), were significantly stimulated by CoQ10. In comparison to controls a significantly increased SOD2 expression was detected in the H2O2 group (1.43-fold; p=0.04), which was prevented by CoQ10 treatment (p=0.04).
Conclusions :
Our results indicate a potential neuroprotective role of CoQ10 in the retina. Thereby, CoQ10 seems to protect RGCs by apoptosis inhibition, activation of intracellular protection cascades, and reduction of mitochondrial stress level.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.