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The Journal of Neuroscience, January 3, 2007, 27(1):203-211; doi:10.1523/JNEUROSCI.0445-06.2007

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Development/Plasticity/Repair
Nonredundant Role of Akt2 for Neuroprotection of Rod Photoreceptor Cells from Light-Induced Cell Death

Guiyuan Li,^1,3 Robert E. Anderson,^1,2,3 Hiroshi Tomita,⁶ Ruben Adler,^4,5 Xiaochun Liu,⁴ Donald J. Zack,^4,5 and Raju V. S. Rajala^1,2,3

Departments of ¹Cell Biology and ²Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, ³Dean McGee Eye Institute, Oklahoma City, Oklahoma 73104, Departments of ⁴Ophthalmology and ⁵Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, and ⁶Division of Biofunctional Science, Tohoku University Biomedical Engineering Research Organization, Sendai 980-8575, Japan

Correspondence should be addressed to Dr. Robert E. Anderson, 608 Stanton L. Young Boulevard, Oklahoma City, OK 73104. Email: robert-anderson{at}ouhsc.edu

The Akt kinases mediate cell survival through phosphorylation and inactivation of apoptotic machinery components. Akt signaling provides a trophic signal for transformed retinal neurons in culture, but the in vivo role of Akt activity is unknown. In this study, we found that all three Akt isoforms were expressed in rod photoreceptor cells. We investigated the functional roles of Akt1 and Akt2, two of the isoforms of Akt, and their biological significance in light-induced retinal degeneration. Consistent with the hypothesis that Akt activity is important to circumvent stress-induced apoptosis, herein we report the novel finding that rod photoreceptor cells in Akt2 knock-out mice exhibited a significantly greater sensitivity to stress-induced cell death than rods in heterozygous or wild-type mice. Under similar conditions, Akt1 deletion had no effect on the retina. The presence of three Akt isoforms in the retina is suggestive of a functional redundancy; however, our studies clearly demonstrate that, under stress, Akt1 and Akt3 cannot complement the specific survival signals driven by Akt2. Furthermore, we show that Akt2 is specially activated is response to light stress. The results presented in this study provide the first direct evidence that Akt2 has a nonredundant neuroprotective role in photoreceptor survival and maintenance.

Key words: Akt/PKB; retina; photoreceptor degeneration; knock-out mice; light damage; apoptosis

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Received Dec. 9, 2005; revised Oct. 18, 2006; accepted Nov. 28, 2006.

Correspondence should be addressed to Dr. Robert E. Anderson, 608 Stanton L. Young Boulevard, Oklahoma City, OK 73104. Email: robert-anderson{at}ouhsc.edu

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