DNA and RNA oxidative damage in the retina is associated with ganglion cell mitochondria.

Autor: Gu L; Stein Eye Institute, University of California, Los Angeles, 100 Stein Plaza, Los Angeles, CA, 90095, USA., Kwong JM; Stein Eye Institute, University of California, Los Angeles, 100 Stein Plaza, Los Angeles, CA, 90095, USA., Caprioli J; Stein Eye Institute, University of California, Los Angeles, 100 Stein Plaza, Los Angeles, CA, 90095, USA.; Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA., Piri N; Stein Eye Institute, University of California, Los Angeles, 100 Stein Plaza, Los Angeles, CA, 90095, USA. piri@jsei.ucla.edu.; Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA. piri@jsei.ucla.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 May 24; Vol. 12 (1), pp. 8705. Date of Electronic Publication: 2022 May 24.
DOI: 10.1038/s41598-022-12770-9
Abstrakt: This study examines retinas from a rat glaucoma model for oxidized nucleosides 8OHdG and 8OHG, biomarkers for oxidative damage of DNA and RNA, respectively. Immunohistochemical data indicate a predominant localization of 8OHdG/8OHG in retinal ganglion cells (RGCs). The levels for these oxidized DNA/RNA products were 3.2 and 2.8 fold higher at 1 and 2 weeks after intraocular pressure elevation compared to control retinas, respectively. 8OHdG/8OHG were almost exclusively associated with mitochondrial DNA/RNA: ~ 65% of 8OHdG/8OHG were associated with RNA isolated from mitochondrial fraction and ~ 35% with DNA. Furthermore, we analyzed retinas of the rd10 mouse, a model for retinitis pigmentosa, with severe degeneration of photoreceptors to determine whether high levels of 8OHdG/8OHG staining intensity in RGCs of control animals is related to the high level of mitochondrial oxidative phosphorylation necessary to support light-evoked RGC activity. No significant difference in 8OHdG/8OHG staining intensity between control and rd10 mouse retinas was observed. The results of this study suggest that high levels of 8OHdG/8OHG in RGCs of wild-type animals may lead to cell damage and progressive loss of RGCs observed during normal aging, whereas ocular hypertension-induced increase in the level of oxidatively damaged mitochondrial DNA/RNA could contribute to glaucomatous neurodegeneration.
(© 2022. The Author(s).)
Databáze: MEDLINE
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