Environmental damage to the retina and preconditioning: Contrasting effects of light and hyperoxic stress

Yuan Zhu*, Krisztina Valter, Jonathan Stone

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)


    PURPOSE. Environmental stress (bright light, hypoxia) can "condition" retinal photoreceptors, increasing their resistance to subsequent stress. The present study tests whether another photoreceptor-lethal stress, hyperoxia, can induce similar resistance. METHODS. Vulnerability to hyperoxia was tested in young adult C57BL/6J mice exposed to 1000 lux cyclic light for 1 week or to 50% O2 for 1 week and then to 75% O2 for 2 weeks. Vulnerability to light was tested in Balb/cJ mice exposed to 300 lux cyclic light for 2 days or to 75% O2 for 2 weeks and then to 1000 lux cyclic light for 1 week. Retinas were analyzed for photoreceptor death, levels of stress-related proteins (GFAP, FGF-2, MnSOD, acrolein), and the regulation of candidate neuroprotective genes (HSP70.1, Ledgf, FGF-13, Timp2). RESULTS. Light preconditioning did not cause measurable death of photoreceptors but reduced photoreceptor death induced by subsequent hyperoxic or light stress, reduced levels of stress-related proteins, and maintained the length and organization of photoreceptor outer segments. Hyperoxic preconditioning caused measurable cell death but provided no protection against subsequent hyperoxic or light stress. Of the four candidate neuroprotective proteins examined, the regulation of only one (Timp2) seemed associated with the neuroprotection observed. CONCLUSIONS. Light preconditioning, causing only minimal damage to photoreceptors, induced protection against subsequent stress from both hyperoxia and light. By contrast, hyperoxic preconditioning caused measurable photoreceptor damage but induced no protection against light or hyperoxia. These data suggest a separation between stress-induced damage to photoreceptors and the upregulation of protective mechanisms, encouraging the search for ways to protect the retina without damaging it.

    Original languageEnglish
    Pages (from-to)4821-4830
    Number of pages10
    JournalInvestigative Ophthalmology and Visual Science
    Issue number9
    Publication statusPublished - Sept 2010


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