Enhanced survival of melanopsin-expressing retinal ganglion cells after injury is associated with the PI3 K/Akt pathway.
In the present study, we studied the factors that contribute to the injury-resistant property of melanopsin-expressing retinal ganglion cells (mRGCs). Since phosphatidylinositol-3 kinase (PI3 K)/Akt signaling pathway is one of the well-known pathways for neuronal cell survival, we investigated the survival of mRGCs by applying the PI3 K/Akt specific inhibitors after injury. Two injury models, unilateral optic nerve transection and ocular hypertension, were adopted using Sprague-Dawley rats. Inhibitors of PI3 K/Akt were injected intravitreally following injuries to inhibit the PI3 K/Akt signaling pathway. Retinas were dissected after designated survival time, immunohistochemistry was carried out to visualize the mRGCs using melanopsin antibody and the number of mRGCs was counted. Co-expression of melanopsin and phospho-Akt (pAkt) was also examined. Compared to the survival of non-melanopsin-expressing RGCs, mRGCs showed a marked resistance to injury and co-expressed pAkt. Application of PI3 K/Akt inhibitors decreased the survival of mRGCs after injury. Our previous study has shown that mRGC are less susceptible to injury following the induction of ocular hypertension. In this study, we report that mRGCs were injury-resistant to a more severe type of injury, the optic nerve transection. More importantly, the PI3 K/Akt pathway was found to play a role in maintaining the survival of mRGCs after injury.
Li
Suk-Yee
SY
Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Yau
Suk-Yu
SY
Chen
Bai-Yu
BY
Tay
David K
DK
Lee
Vincent W H
VW
Pu
Ming-Liang
ML
Chan
Henry H L
HH
So
Kwok-Fai
KF
D000818:Animals; D019771:Axotomy; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D007267:Injections; D020221:Optic Nerve Injuries; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D017299:Rod Opsins / Q000378:metabolism*; D013477:Superior Colliculi / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D000099210:Melanopsin
D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D017299:Rod Opsins; D000099210:Melanopsin