Photoreceptor oxidative stress in hyperoxia-induced proliferative retinopathy accelerates rd8 degeneration

Michelle Lajko, Herminio J. Cardona, Joann M. Taylor, Kathryn N. Farrow, Amani A. Fawzi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


To investigate the impact of photoreceptor oxidative stress on photoreceptor degeneration in mice carrying the rd8 mutation (C57BL/6N). We compared the hyperoxia-induced proliferative retinopathy (HIPR) model in two mouse strains (C57BL/6J and C57BL/6N). Pups were exposed to 75% oxygen, starting at birth and continuing for 14 days (P14). Mice were eutha-nized at P14, or allowed to recover in room air for one day (P15), seven days (P21), or 14 days (P28). We quantified retinal thickness and the length of residual photoreceptors not affected by rosette formation. In addition we explored differences in retinal immunostaining for NADPH oxidase 4 (NOX4), Rac1, vascular endothelium, and activated Müller cells. We analyzed photoreceptor oxidative stress using DCF staining in cross sections and quantified NOX4 protein levels using western blotting. C57BL/6N mice in HIPR showed increased oxidative stress, NOX4, and Rac1 in the photoreceptors at P14 and P15 compared to C57BL/ 6J. In addition, we observed significant progression of photoreceptor degeneration, with significantly accelerated rosette formation in C57BL/6N under HIPR, compared to their room air counterparts. Furthermore, C57BL/6N under HIPR had significantly thinner central retinas than C57BL/6J in HIPR. We did not find a difference in vascular disruption or Müller cell activation comparing the two strains in hyperoxia. In HIPR, the C57BL/6N strain carrying the rd8 mutation showed significantly accelerated photoreceptor degeneration, mediated via exacerbated photoreceptor oxidative stress, which we believe relates to Rac1-NOX dysregulation in the setting of Crb1 loss-of-function.

Original languageEnglish (US)
Article numbere0180384
JournalPloS one
Issue number7
StatePublished - Jul 2017

ASJC Scopus subject areas

  • General


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