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Maria Miranda, Laura Trachsel-Moncho, Soledad Benlloch-Navarro, Michael Grima, Inmaculada Almansa, Javier Araiz, Enric Poch; Oxidative stress and autophagy markers in rd10 mice retina. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2262.
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© ARVO (1962-2015); The Authors (2016-present)
Oxidative stress has been associated with many retinal diseases including retinitis pigmentosa (RP). Increased oxidative stress can induce lipid, protein and DNA changes which may be irreversible, leading to retinal cell death. These damaged cellular components should be degraded by different systems, including autophagy, which can be triggered by oxidative stress. Autophagy is a highly conserved lysosomal pathway, which is crucial for maintaining cellular homeostasis and cell survival under stressful conditions. For the last years, accumulating data has pointed to an essential role of reactive oxygen species (ROS) in the activation of autophagy. Therefore, oxidative stress and autophagy may be important factors in the pathogenesis of RP. The aim of this work was to study changes in different markers of oxidative stress in the retina of a RP animal model.
Animals were treated in accordance to the ARVO statement for the use of animals in ophthalmic and vision research. We obtained retinas from C57BL and rd10 mice at different postnatal days (PN 13, 21, and 28). Malondialdehyde (MDA) and nNOS (neuronal nitric oxide synthase) was determined by HPLC and immunohistochemistry. Western blot analysis was performed to assess microtubule-associated protein 1 light chain 3 II/I (LC3II/I) ratio, Beclin and lysosomal associated membrane protein-2 (LAMP2A).
At PN21 (which was the peak of cell death as determined by TUNEL) there was a significant increase in MDA and nNOS in the retina of rd10 mice compared to control ones (p<0,05). The increase in nNOS was particularly notable in the peripheral retina (2-fold increase). These results confirm the importance of oxidative stress in RP. No changes were observed in Beclin for both control and rd10 mice. LC3II/I ratio and LAMP2A (autophagy markers) expression increased both in control and rd10 mice with age (with a statistically difference between P13 and P28 for LC3II/I and LAMP-2A’ score, p <0.05), however the pattern of increase was different in rd10 mice.
Further studies are needed to clarify autophagy role in RP. However, drugs that could target at the same time oxidative stress and autophagy may be new strategies in RP treatment.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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