April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Autophagy and the Control of Photoreceptor Apoptosis
Author Affiliations & Notes
  • C. G. Besirli
    Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan
  • N. D. Chinskey
    Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan
  • Q.-D. Zheng
    Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan
  • D. N. Zacks
    Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan
  • Footnotes
    Commercial Relationships  C.G. Besirli, None; N.D. Chinskey, None; Q.-D. Zheng, None; D.N. Zacks, None.
  • Footnotes
    Support  The Michigan Eye Bank
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 5207. doi:
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    • Get Citation

      C. G. Besirli, N. D. Chinskey, Q.-D. Zheng, D. N. Zacks; Autophagy and the Control of Photoreceptor Apoptosis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5207.

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

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Purpose: : To determine the role of autophagy activation during retinal detachment-induced photoreceptor apoptosis.

Methods: : Retina-RPE separation was created in Brown Norway rats by subretinal injection of 1% hyaluronic acid. The expression of LC3 in the retina and the time course of LC3B-I to LC3B-II conversion after retinal detachment were determined with Western blots and immunohistochemistry. LC3B-I to LC3B-II conversion was examined in the presence of Met12, a small molecule inhibitor of the Fas/FasL signaling. The activation of cathepsin B and cathepsin D in photoreceptors after retinal detachment was measured with Western blots. In some animals, retinal detachments were created with or without subretinal injection of 3-methyladenine (3-MA) or vehicle alone. Caspase-8 activation was examined with immunohistochemistry after retinas were harvested. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) was performed in retinal sections 1, 3, and 7 days after separation.

Results: : Retina-RPE separation resulted in increased conversion of LC3B-I to LC3B-II in detached photoreceptors. This increase in LC3B-II levels was Fas-dependent as it was reduced in the presence of Met12. Detached retinas had increased levels of autophagosome-associated lysosomal proteases, cathepsin B and cathepsin D. Inhibition of autophagy by 3-MA in detached retinas accelerated the time course of photoreceptor caspase 8 activation and TUNEL labeling.

Conclusions: : Fas-receptor activation after retina-RPE separation results in activation of both autophagy and apoptosis cascades. The autophagy cascade appears to function as a negative regulator (inhibitor) of the Fas-mediated apoptosis cascade.

Keywords: apoptosis/cell death • cell survival • photoreceptors 

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