June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Akt2 signaling in diabetes-induced dysfunction of the outer blood retina barrier
Rachel Daley; Sayan Ghosh; PENG SHANG; Nadezda A Stepicheva; Anastasiia Strizhakova; Olivia Chowdhury; Victoria Koontz; Stacey L Hose; J. Samuel Zigler; Debasish Sinha; Haitao Liu
Author Affiliations & Notes
  • Rachel Daley
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Sayan Ghosh
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • PENG SHANG
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Nadezda A Stepicheva
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Anastasiia Strizhakova
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Olivia Chowdhury
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Victoria Koontz
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Stacey L Hose
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • J. Samuel Zigler
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Debasish Sinha
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Haitao Liu
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Rachel Daley None; Sayan Ghosh None; PENG SHANG None; Nadezda Stepicheva None; Anastasiia Strizhakova None; Olivia Chowdhury None; Victoria Koontz None; Stacey Hose None; J. Zigler None; Debasish Sinha None; Haitao Liu None
  • Footnotes
    Support  This work was supported by start-up funds to DS from Ophthalmology, University of Pittsburgh, the Jennifer Salvitti Davis, M.D. Chair Professorship in Ophthalmology (DS) and Research to Prevent Blindness (Ophthalmology, UPMC).
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 3599 – A0054. doi:
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      Rachel Daley, Sayan Ghosh, PENG SHANG, Nadezda A Stepicheva, Anastasiia Strizhakova, Olivia Chowdhury, Victoria Koontz, Stacey L Hose, J. Samuel Zigler, Debasish Sinha, Haitao Liu; Akt2 signaling in diabetes-induced dysfunction of the outer blood retina barrier. Invest. Ophthalmol. Vis. Sci. 2022;63(7):3599 – A0054.

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Abstract

Purpose : Diabetic Retinopathy (DR) is a significant complication of diabetes that causes blindness in adults. DR is also associated with the disintegration of the blood-retina barrier (BRB). The altered inner BRB formed by endothelial cells in the plexiform layers has been investigated broadly in DR pathogenesis; however, in DR the malfunction of the outer BRB consisting of retinal pigment epithelium (RPE) and choroid has rarely been studied. This study investigates the potential role of Akt2 in the diabetes-induced breakdown of the outer BRB in RPE cells.

Methods : Best1-Cre generated RPE-specific Akt2 conditional knockout (cKO) mice were used. Rodent body weights and blood glucose levels were monitored while diabetes was induced in Akt2fl/fl and Akt2 cKO mice by intraperitoneal injection of Streptozotocin for 5 consecutive days. The mice were sacrificed after an 8 month duration of diabetes (10 months of age), and HbA1c, tight junction proteins, and epithelial-mesenchymal transition (EMT) markers were examined.

Results : Blood glucose and HbA1c were elevated in diabetic Akt2fl/fl and Akt2 cKO mice. Akt2fl/fl and Akt2 cKO diabetic mice exhibited significantly lower body weights than appropriate non-diabetic controls. After 8 months of diabetes, the Akt2fl/fl mice showed a diabetes-induced reduction of the RPE tight junction protein ZO-1 and adherence junction proteins occludin and E-cadherin; Both RNA and protein levels of the EMT markers SNAIL/SLUG and TWIST were elevated in the RPE cells of Akt2fl/fl diabetic mice compared to Akt2fl/fl non-diabetic mice, while such alterations were inhibited in Akt2 cKO diabetic mice. Vimentin was elevated in the RPE of Akt2fl/fl diabetic mice and was decreased in Akt2 cKO diabetic mice. The junction proteins and EMT markers in the non-diabetic control groups showed no significant changes.

Conclusions : Deletion of Akt2 in the RPE prevents diabetes-induced alterations in outer BRB and inhibits diabetes-induced elevation of EMT markers.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Attribution-NonCommercial-NoDerivatives
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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