Purchase this article with an account.
H. Imai, P. E. Fort, M. K. Losiewicz, T. W. Gardner; IGF-2 Provides Anti-Apoptotic Effects in Diabetic Retina and Retinal Neuroglial Cells via PI3-Kinase/Akt Dependent Pathway. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4988.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To investigate whether IGF-2 has an anti-apoptotic effect both in retinal neuroglial cells in culture and in diabetic retinas.
Differentiated R28 cells were serum-deprived for 24 hours and treated with the PI3-K inhibitor LY294002 or the dual PI3-K and mTOR inhibitor PI103, followed by addition of 10nM IGF-2. After the treatment, immunocytochemistry against cleaved caspase-3 in a combination with Hoechst nuclear staining was performed. The number of cleaved caspase-3 immunoreactive and pyknotic cells were summed and expressed as percentage of the number of cleaved caspase-3 immunoreactive or pyknotic cells/total number of cells × 100. Streptozotocin induced 4 week diabetic rats were treated with/without the intravitreal IGF-2 injection (5 µl of 1 µM IGF-2 solution). Retinas were extracted one hour later and used for Akt-1 kinase activity assay and Western blot for apoptosis related proteins (bax, bcl-2 and bcl-xl).
In the presence of serum, 1% of cells were pyknotic, whereas serum deprivation led to pyknosis in 8% of cells, and IGF-2 treatment significantly (p<0.01) reduced the number of pyknotic cells to about 2%. Both LY294002 and PI103 blocked this effect. Similarly, IGF-2 treatment significantly decreased the number of cleaved caspase-3 immunoreactive cells induced by serum deprivation (4% vs 22%, respectively; p<0.01), and the IGF-2 effect was inhibited by both LY294002 and PI103 (22% vs 17%, respectively). In streptozotocin induced 4 week diabetic rats, Akt-1 kinase activity was reduced by 20% (P<0.05). Both bax and bcl-2 expression were increased, whereas bcl-xl expression was decreased in diabetic retinas, and these changes were normalized by intravitreal IGF-2 injection.
These data suggest that IGF-2 can rescue retinal neurons from apoptosis via the PI-3 kinase/Akt-dependent pathway and may enhance cell survival in retinal neurodegenerations.
This PDF is available to Subscribers Only