Differential roles of phosphatidylinositol 3-kinase/akt pathway in retinal ganglion cell survival in rats with or without acute ocular hypertension

Huang, Yao; Cen, Ling-Ping; Luo, Jian-Min; Wang, N.; Zhang, M.-Z.; Rooijen, Nico van; Pang, Chi Pui; Cui, Qing

doi:10.1016/j.neuroscience.2008.02.007

Cited by 23 publications

(16 citation statements)

References 52 publications

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“…The reported increase of RGC death observed in PI3K inhibitors-treated retinas following optic nerve clamping or retinal ischemia further support the neuroprotective role for the endogenous activation of this pathway (Nakazawa et al, 2003;Huang et al, 2008;Russo et al, 2008a).…”

Section: Endogenous Pro-survival Pathways and Neuroprotectionmentioning

confidence: 53%

New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system

Nucci

Russo

Martucci

et al. 2016

European Journal of Pharmacology

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a b s t r a c tGlaucoma is a disease where retinal ganglion cells (RGC) are specifically affected though a number of evidences endorse the hypothesis that glaucoma is a neuro-degenerative disorder of the central nervous system and suggest a possible connection between glaucomatous damage and cerebrovascular alterations. The mechanisms underlying RGC loss are not yet fully known but alterations of the autophagy machinery have been recently proposed as a potential contributing factor as for Alzheimer's disease.Here we review the current literature on new strategies for neuroprotection in glaucoma, focusing on pharmacologic strategies to minimize RGC damage.

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Section: Endogenous Pro-survival Pathways and Neuroprotectionmentioning

confidence: 53%

New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system

Nucci

Russo

Martucci

et al. 2016

European Journal of Pharmacology

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“…Various growth factors or hormone, such as brain-derived neurotrophic factor (Bonnet et al 2004;Nakazawa et al 2002) and erythropoietin (Weishaupt et al 2004), rescued the injured RGCs via this pathway. Previous studies demonstrated that the injury-mediated activation of PI3 K/Akt pathway probably contributes to the delayed cell death of RGCs after ONT and acute OH (Cheung et al 2004;Huang et al 2008;Nakazawa et al 2002). As anticipated, the surviving mRGCs expressed activated Akt after the injury of ONT.…”

Section: Discussionmentioning

confidence: 98%

Enhanced Survival of Melanopsin-expressing Retinal Ganglion Cells After Injury is Associated with the PI3 K/Akt Pathway

Yau

Chen

et al. 2008

Cell Mol Neurobiol

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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.

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“…Moreover, LncRNA-MALAT1 knockout can lead to the inactivation of the PI3K/Akt signaling pathway [19]. Another study even showed that a low-dose PI3K/Akt pathway inhibitor can inhibit the survival of RGCs in a high IOP group, while high-dose inhibitors have no significant impact on a normal group [44]. Therefore, the PI3K/Akt pathway may affect RGC survival in the context of IOP elevation but not under normal conditions.…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA-MALAT1 Mediates Retinal Ganglion Cell Apoptosis Through the PI3K/Akt Signaling Pathway in Rats with Glaucoma

You

et al. 2017

Cell Physiol Biochem

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Background/Aims: The aim of the present study is to investigate the effect of long non-coding RNA-MALAT1 (LncRNA-MALAT1) on retinal ganglion cell (RGC) apoptosis mediated by the PI3K/Akt signaling pathway in rats with glaucoma. Methods: RGCs were isolated and cultured, and monoclonal antibodies (anti-rat Thy-1, Brn3a and RBPMS) were examined by immunocytochemistry. An overexpression vector MALAT1-RNA activation (RNAa), gene knockout vector MALAT1-RNA interference (RNAi), and control vector MALAT1-negative control (NC) were constructed. A chronic high intraocular pressure (IOP) rat model of glaucoma was established by episcleral vein cauterization. The RGCs were divided into the RGC control, RGC pressure, RGC pressure + MALAT1-NC, RGC pressure + MALAT1-RNAi and RGC pressure + MALAT1-RNAa groups. Sixty Sprague-Dawley (SD) rats were randomly divided into the normal, high IOP, high IOP + MALAT1-NC, high IOP + MALAT1-RNAa and high IOP + MALAT1-RNAi groups. qRT-PCR and western blotting were used to detect the expression levels of LncRNA-MALAT1 and PI3K/Akt. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and flow cytometry were used to detect RGC apoptosis. Results: Immunocytochemistry revealed that the cultured RGCs reached 90% purity. Compared with the RGC pressure + MALAT1-NC group, the RGC pressure + MALAT1-RNAa group exhibited elevated expression levels of MALAT1, lower total protein levels of PI3K and Akt and decreased RGC apoptosis, while these expression levels were reversed in the RGC pressure + MALAT1-RNAi group. RGC numbers and PI3K/Akt expression levels in the high IOP model groups were lower than those in the normal group. In the high IOP + MALAT1-RNAa group, the mRNA and protein expression levels of PI3K/Akt were reduced but higher than those in the other three high IOP model groups. Additionally, RGC numbers in the high IOP + MALAT1-RNAa group were lower than those in the normal group but higher than those in the other three high IOP model groups. Conclusion: Our study provides evidence that LncRNA-MALAT1 could inhibit RGC apoptosis in glaucoma through activation of the PI3K/Akt signaling pathway.

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Differential roles of phosphatidylinositol 3-kinase/akt pathway in retinal ganglion cell survival in rats with or without acute ocular hypertension

Cited by 23 publications

References 52 publications

New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system

New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system

Enhanced Survival of Melanopsin-expressing Retinal Ganglion Cells After Injury is Associated with the PI3 K/Akt Pathway

Long Non-Coding RNA-MALAT1 Mediates Retinal Ganglion Cell Apoptosis Through the PI3K/Akt Signaling Pathway in Rats with Glaucoma

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