Purchase this article with an account.
Matus Rehak, Sindhu Saraswathy, Peter Wiedemann, Narsing A. Rao; Age-dependent Differences In The Activation Of Autophagy In Retinal Ischemia-reperfusion. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4281.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Recent studies suggested that autophagy plays a role in a retinal damage resulting from ischemia-reperfusion (IR). The ageing might influence the total autophagic activity as well as the pathway which leads to the activation of the autophagy. We investigated the age-dependent changes in the activation of autophagy in the murine model of IR.
Two age groups of C57BL/6 mice were investigated. In 34 young mice (4 weeks ) and in 34 old mice (14 months) the unilateral retinal IR was induced by cannulating the anterior chamber of the globe and transiently elevating the intraocular pressure for 60 min. Untreated eyes served as controls. After 1, 4, 12, 24 and 72 hours of reperfusion the animals were sacrificed and the markers of autophagy as light chain 3 (LC3-I and II), beclin-1 and autophagy-related gene 5 (atg-5) as well as calpains and caspase-3 were investigated using western blot techniques and immunohistochemistry. Further, the retinal thickness and histological changes were determined on day 45 after IR.
In both age groups IR resulted in a rapid activation of autophagy revealednby significant increase of LC3-II, beclin-1 and atg-5 detected by western blotting. The highest amount of LC3-II and atg-5 was found in the young mice 12 hours after IR whereas in the old mice 24 hours after IR. The presence of beclin-1 protein was significantly higher in the young mice 4 and 12 hours after IR when compared with old animals. Calpains (1 and 4 hours after IR) and casase-3 (24 hours after IR) showed significantly higher activity in the old animals. On day 45 after IR the reduction of the total retinal thickness was significantly higher in the old mice (145.7±23.8 μm) compared to young mice (202.0±30.8 μm).
Our study showed the age-dependent differences in the activation of the autophagy after retinal ischemia-reperfusion injury. In the young animals the beclin-dependent way leads to significantly faster activation of the autophagy whereas in the old animals the beclin-independent activation seems to play much important role. In the old animals IR leads to the significantly higher activation of the caspase-3 and the retinal atrophy.
This PDF is available to Subscribers Only