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Hong Zhu, Fenghua Wang, Xiaodong Sun; Inhibition of autophagy by 3MA enhances the effect of ERS-mediated apoptosis in photoreceptors after experimental retinal detachment. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2871.
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Detachment of photoreceptors from retinal pigment epithelium is seen in various retinal diseases such as retinal detachment and age-related macular degeneration that leads to loss of vision. Homeostatic control, such as autophagy, may prevent this outcome. This study tests whether autophagy can protect photoreceptors from cell death and further examined the relationship between autophagy and endoplasmic reticulum stress (ERS)-mediated apoptosis after experimental retinal detachment in rats.
Retinal detachment was created in Sprague-Dawley rats by subretinal injection of hyaluronic acid. Autophagy was inhibited using 3-methyladenine (3MA) and the effect on ERS-mediated apoptosis was measured using a caspase12 activity assay and TUNEL staining. Photoreceptor damage was evaluated by measuring the outer nuclear layer (ONL) thickness. ER stress and autophagy levels were also quantified.
The peak period of autophagy activity occurs about 1day after detachment, prior to the peak period of apoptosis. Inhibition of autophagy accelerated the time course of caspase12 activation, significantly increased ERS damage according to evaluation of CHOP, and enhanced accumulation of unfolded protein represented by LAMP-2A. 3 day after detachment, 3MA increased photoreceptor TUNEL-positive staining compared to vehicle (9.44 ± 0.32 % vs. 3.93 ± 0.51 %, t = -25.736, P = 0.000) and increased the reduction of ONL thickness (49.63 ± 3.54 μm vs. 57.50 ± 3.21 μm, t = 4.661, P = 0.000).
Autophagy participated apoptosis in ERS-mediated photoreceptor death after experiment retinal detachment. Regulating autophagy may be used as a novel therapeutic strategy for preventing vision loss in diseases characterized by photoreceptor detachment.
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