June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Inhibition of autophagy by 3MA enhances the effect of ERS-mediated apoptosis in photoreceptors after experimental retinal detachment
Author Affiliations & Notes
  • Hong Zhu
    Department of Ophthalmology, Shanghai First People’s Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China
    Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
  • Fenghua Wang
    Department of Ophthalmology, Shanghai First People’s Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China
  • Xiaodong Sun
    Department of Ophthalmology, Shanghai First People’s Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China
  • Footnotes
    Commercial Relationships Hong Zhu, None; Fenghua Wang, None; Xiaodong Sun, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 2871. doi:
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    • Get Citation

      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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

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.

 
Methods
 

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.

 
Results
 

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).

 
Conclusions
 

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.

     
Keywords: 697 retinal detachment • 648 photoreceptors • 426 apoptosis/cell death  
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