Intrinsic activation of PI3K/Akt signaling pathway and its neuroprotective effect against retinal injury.
OBJECTIVE
The aim of this study was to determine whether the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway can function as a neuroprotective pathway following induced retinal injury.


METHODS
The activation of Akt was assessed by immunoblot analysis, and the role of PI3K/Akt pathway was evaluated by TUNEL staining and counting the number of retrogradely-labeled retinal ganglion cells (RGCs) in the whole retina at 168 h after injury with or without PI3K specific inhibitor, LY294002.


RESULTS
Akt was induced within one hr and reached a maximum 6 hrs after optic nerve clamping. The activation was observed in the RGC layer including RGCs, the inner plexiform layer, inner nuclear layer, and in the photoreceptor outer segments. The number of surviving RGCs was decreased significantly 168 hrs after injury. LY294002 partially inhibited the activation of Akt, and significantly decreased the number of surviving RGCs as compared with that of injury alone.


CONCLUSIONS
These results indicate that the PI3K/Akt signaling pathway is activated intrinsically and has a neuroprotective effect on injured RGCs.
Nakazawa
Toru
T
Department of Ophthalmology, Tohoku University School of Medicine, Sendai, Japan. ntoru@fa2.so-net.ne.jp
Shimura
Masahiko
M
Tomita
Hiroshi
H
Akiyama
Hiroshi
H
Yoshioka
Yuki
Y
Kudou
Hideyo
H
Tamai
Makoto
M
D000818:Animals; D002452:Cell Count; D002470:Cell Survival; D002867:Chromones / Q000494:pharmacology; D003250:Constriction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D007511:Ischemia / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009900:Optic Nerve; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000473:pathology / Q000502:physiology; D012171:Retinal Vessels / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology*; D013194:Staining and Labeling; D013266:Stilbamidines
D002867:Chromones; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D013266:Stilbamidines; C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494920:Akt1 protein, rat