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