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An imbalance in autophagy contributes to retinal damage in a rat model of oxygen-induced retinopathy |
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| Authors: | Noemi Anna Pesce Alessio Canovai Flavia Plastino Emma Lardner Anders Kvanta Maurizio Cammalleri Helder André Massimo Dal Monte |
| Affiliation: | 1. Department of Biology, University of Pisa, Pisa, Italy Department of Clinical Neuroscience, Division of Eye and Vision, St Erik Eye Hospital, Karolinska Institutet, Solna, Sweden Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Visualization (equal), Writing - original draft (equal);2. Department of Biology, University of Pisa, Pisa, Italy Contribution: Formal analysis (equal), Investigation (equal), Visualization (equal), Writing - original draft (equal);3. Department of Clinical Neuroscience, Division of Eye and Vision, St Erik Eye Hospital, Karolinska Institutet, Solna, Sweden Contribution: Formal analysis (supporting), Investigation (supporting), Visualization (supporting), Writing - original draft (supporting);4. Department of Clinical Neuroscience, Division of Eye and Vision, St Erik Eye Hospital, Karolinska Institutet, Solna, Sweden Contribution: Investigation (supporting);5. Department of Clinical Neuroscience, Division of Eye and Vision, St Erik Eye Hospital, Karolinska Institutet, Solna, Sweden Contribution: Supervision (supporting);6. Department of Biology, University of Pisa, Pisa, Italy Contribution: Formal analysis (supporting), Investigation (supporting), Visualization (supporting);7. Department of Clinical Neuroscience, Division of Eye and Vision, St Erik Eye Hospital, Karolinska Institutet, Solna, Sweden Contribution: Conceptualization (equal), Funding acquisition (supporting), Project administration (equal), Supervision (equal), Writing - review & editing (equal);8. Department of Biology, University of Pisa, Pisa, Italy |
| Abstract: | In retinopathy of prematurity (ROP), the abnormal retinal neovascularization is often accompanied by retinal neuronal dysfunction. Here, a rat model of oxygen-induced retinopathy (OIR), which mimics the ROP disease, was used to investigate changes in the expression of key mediators of autophagy and markers of cell death in the rat retina. In addition, rats were treated from birth to postnatal day 14 and 18 with 3-methyladenine (3-MA), an inhibitor of autophagy. Immunoblot and immunofluorescence analysis demonstrated that autophagic mechanisms are dysregulated in the retina of OIR rats and indicated a possible correlation between autophagy and necroptosis, but not apoptosis. We found that 3-MA acts predominantly by reducing autophagic and necroptotic markers in the OIR retinas, having no effects on apoptotic markers. However, 3-MA does not ameliorate retinal function, which results compromised in this model. Taken together, these results revealed the crucial role of autophagy in retinal cells of OIR rats. Thus, inhibiting autophagy may be viewed as a putative strategy to counteract ROP. |
| Keywords: | autophagy cell death necroptosis oxygen-induced retinopathy rat model retinopathy of prematurity |