May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Diabetes Increases Retinal Autophagy; Reversal With Low Dose Periocular Insulin
Author Affiliations & Notes
  • R. S. Singh
    Ophthalmology, Penn State College of Medicine, Hershey, Pennsylvania
    Internal Medicine, Penn State Milton S Hershey Medical Center, Hershey, Pennsylvania
  • P. Fort
    Ophthalmology, Penn State College of Medicine, Hershey, Pennsylvania
  • M. Losiewicz
    Ophthalmology, Penn State College of Medicine, Hershey, Pennsylvania
  • T. W. Gardner
    Ophthalmology, Penn State College of Medicine, Hershey, Pennsylvania
  • Footnotes
    Commercial Relationships  R.S. Singh, None; P. Fort, None; M. Losiewicz, None; T.W. Gardner, None.
  • Footnotes
    Support  JDRF
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1536. doi:https://doi.org/
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      R. S. Singh, P. Fort, M. Losiewicz, T. W. Gardner; Diabetes Increases Retinal Autophagy; Reversal With Low Dose Periocular Insulin. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1536. doi: https://doi.org/.

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

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Abstract

Purpose: : We have shown previously that diabetes rapidly impairs retinal insulin receptor and Akt signaling, with decreased retinal protein synthesis and accelerated retinal neuronal apoptosis. Hence, we hypothesized that diabetes also induces autophagy in the retina.

Methods: : Autphagy markers were studied in serum-deprived R28 rat retinal cells, and in retinas from control and diabetic rats with or without subconjunctivally injected insulin. Beclin-1and Atg-6 were analyzed using immunoblotting and immunohistochemistry. Lysosomal function was assessed by staining for acid phosphatase and immunoblotting for lysosomal enzymes such as cathepsin D. Proteins that influence the rate of autophagy such as Akt and BCl-2 were also quantified.

Results: : R28 cells exhibit increased expression of beclin-1 after 2 hours of serum deprivation. The retina shows an increased beclin-1 immunostaining along with prominent acid phosphatase staining after 4 weeks of diabetes. mRNA level of lysosomal proteases is increased in early diabetes along with increased Cathepsin D protein expression and 4 days of low dose subconjunctival insulin treatment reverses this increase. BCL-2 levels are decreased with diabetes and Atg-5 is cleaved into the pro-apoptotic 24kDa fragment; subconjunctival insulin treatment reverses this change. Subconjunctival insulin treatment also normalizes the reduced Akt kinase activity seen in the diabetic retina.

Conclusions: : These findings suggest that autophagy is rapid retinal response to the metabolic stress of insulin deficiency and may participate in retinal neurodegenration.

Keywords: diabetic retinopathy • apoptosis/cell death • stress response 
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