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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.
Neuroscience. 2008 Apr 22; 153(1):214-25.N

Abstract

Intraocular pressure (IOP) elevation has often been used as an experimental model to study mechanisms underlying retinal ganglion cell (RGC) death associated with ocular ischemic injury and glaucoma. The aim of the present study, using both in vitro and in vivo approaches, was to investigate the role of phosphatidylinositol 3-kinase (PI3K)/akt pathway in RGC viability in normal rats and rats following transient IOP elevation. For in vivo studies, pathway inhibitors were administered intravitreally on days 3, 9, and 15 post-2-h IOP elevation at 110 mm Hg. Toward the end of the 3-week examination period, the fluorescent dye Fluorogold was used to retrogradely label surviving RGCs. In order to examine the role of macrophages that were recruited into the eye following the pathway inhibition, clodronate liposomes were used to deplete phagocytic cells in the eye. PI3K/akt pathway activity and location in the retina were examined using Western blot and immunohistochemistry, respectively. Here we showed that PI3K/akt inhibitors 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) and KY12420 at low concentrations (2 microM or 20 microM) did not influence RGC survival but caused RGC loss at high concentration (200 muM) in retinal explants derived from intact rats. In contrast, both LY294002 and KY12420 at 20 microM led to RGC loss in retinal explants derived from IOP-elevated eyes. A detrimental action of phagocytic cells on RGC survival was also seen in these retinas. In vivo results confirmed the detrimental actions of PI3K/akt inhibition and macrophages on RGC survival in IOP-elevated, but not intact eyes even with high concentration of LY294002. Low level of PI3K/akt activity was detected in the ganglion cell layer (GCL) in intact retina. Acute IOP elevation activated PI3K/akt pathway in the inner nuclear layer and GCL including RGCs. This study thus demonstrates that PI3K/akt pathway mediates RGC survival after IOP elevation but not under normal condition.

Authors+Show Affiliations

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, 147K Argyle Street, Kowloon, Hong Kong, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18358617

Citation

Huang, Y, et al. "Differential Roles of Phosphatidylinositol 3-kinase/akt Pathway in Retinal Ganglion Cell Survival in Rats With or Without Acute Ocular Hypertension." Neuroscience, vol. 153, no. 1, 2008, pp. 214-25.
Huang Y, Cen LP, Luo JM, et al. Differential roles of phosphatidylinositol 3-kinase/akt pathway in retinal ganglion cell survival in rats with or without acute ocular hypertension. Neuroscience. 2008;153(1):214-25.
Huang, Y., Cen, L. P., Luo, J. M., Wang, N., Zhang, M. Z., van Rooijen, N., Pang, C. P., & Cui, Q. (2008). Differential roles of phosphatidylinositol 3-kinase/akt pathway in retinal ganglion cell survival in rats with or without acute ocular hypertension. Neuroscience, 153(1), 214-25. https://doi.org/10.1016/j.neuroscience.2008.02.007
Huang Y, et al. Differential Roles of Phosphatidylinositol 3-kinase/akt Pathway in Retinal Ganglion Cell Survival in Rats With or Without Acute Ocular Hypertension. Neuroscience. 2008 Apr 22;153(1):214-25. PubMed PMID: 18358617.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential roles of phosphatidylinositol 3-kinase/akt pathway in retinal ganglion cell survival in rats with or without acute ocular hypertension. AU - Huang,Y, AU - Cen,L-P, AU - Luo,J-M, AU - Wang,N, AU - Zhang,M-Z, AU - van Rooijen,N, AU - Pang,C P, AU - Cui,Q, Y1 - 2008/02/19/ PY - 2007/04/27/received PY - 2008/02/04/revised PY - 2008/02/05/accepted PY - 2008/3/25/pubmed PY - 2008/8/19/medline PY - 2008/3/25/entrez SP - 214 EP - 25 JF - Neuroscience JO - Neuroscience VL - 153 IS - 1 N2 - Intraocular pressure (IOP) elevation has often been used as an experimental model to study mechanisms underlying retinal ganglion cell (RGC) death associated with ocular ischemic injury and glaucoma. The aim of the present study, using both in vitro and in vivo approaches, was to investigate the role of phosphatidylinositol 3-kinase (PI3K)/akt pathway in RGC viability in normal rats and rats following transient IOP elevation. For in vivo studies, pathway inhibitors were administered intravitreally on days 3, 9, and 15 post-2-h IOP elevation at 110 mm Hg. Toward the end of the 3-week examination period, the fluorescent dye Fluorogold was used to retrogradely label surviving RGCs. In order to examine the role of macrophages that were recruited into the eye following the pathway inhibition, clodronate liposomes were used to deplete phagocytic cells in the eye. PI3K/akt pathway activity and location in the retina were examined using Western blot and immunohistochemistry, respectively. Here we showed that PI3K/akt inhibitors 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) and KY12420 at low concentrations (2 microM or 20 microM) did not influence RGC survival but caused RGC loss at high concentration (200 muM) in retinal explants derived from intact rats. In contrast, both LY294002 and KY12420 at 20 microM led to RGC loss in retinal explants derived from IOP-elevated eyes. A detrimental action of phagocytic cells on RGC survival was also seen in these retinas. In vivo results confirmed the detrimental actions of PI3K/akt inhibition and macrophages on RGC survival in IOP-elevated, but not intact eyes even with high concentration of LY294002. Low level of PI3K/akt activity was detected in the ganglion cell layer (GCL) in intact retina. Acute IOP elevation activated PI3K/akt pathway in the inner nuclear layer and GCL including RGCs. This study thus demonstrates that PI3K/akt pathway mediates RGC survival after IOP elevation but not under normal condition. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/18358617/Differential_roles_of_phosphatidylinositol_3_kinase/akt_pathway_in_retinal_ganglion_cell_survival_in_rats_with_or_without_acute_ocular_hypertension_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(08)00217-0 DB - PRIME DP - Unbound Medicine ER -