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JAK/STAT pathway mediates retinal ganglion cell survival after acute ocular hypertension but not under normal conditions.
Exp Eye Res. 2007 Nov; 85(5):684-95.EE

Abstract

Intraocular pressure (IOP) elevation is an important cause of glaucoma. Animal models of ocular hypertension have been widely used to mimic glaucoma to investigate the mechanisms underlying retinal ganglion cell (RGC) death and search for possible cure. The aim of the present study was to examine the role of JAK/STAT pathway in RGC viability in normal condition or after acute IOP elevation. Retinal explants obtained from intact or IOP-elevated eyes were firstly used to examine the effect of the JAK/STAT pathway inhibitors, AG490 and Jak Inhibitor I, on RGC viability in vitro. The role of this signal pathway was further investigated and confirmed in vivo. AG490 and Jak Inhibitor I were applied into the left eye on days 3, 9, and 15 post 2-h IOP elevation at 110mmHg. Fluorescence dye Fluorogold was used to retrogradely label surviving RGCs. Because macrophage recruitment was seen in the IOP-elevated eyes after inhibition of this pathway, clodronate liposomes were used to remove phagocytic cells in the eye and examine the role of JAK/STAT pathway in RGC survival independent of macrophages. Activities and location of JAK/STAT pathway in the retina were examined using Western blotting and immunohistochemistry. We found that inhibition of JAK/STAT pathway did not affect RGC survival in the retinal explants derived from intact eye but caused RGC death in the retinal explants that were derived from IOP-elevated eye. Importantly, the detrimental effect of JAK/STAT pathway inhibition on RGC survival was also observed in vivo following acute IOP elevation, but not in intact eye. In addition, both in vitro and in vivo experiments confirmed a detrimental action of phagocytic cells following acute IOP elevation and the pathway inhibition. Compatible with what were observed in vivo, Western blotting and immunohistochemistry showed that JAK/STAT activities were not present in intact retina, but acute IOP elevation activated JAK/STAT pathway in the retina, in the regions of inner nuclear layer and ganglion cell layer, including RGCs. The IOP elevation-induced JAK/STAT activities were effectively abolished by intravitreal application of AG490. This study thus shows that (1) acute IOP elevation activates JAK/STAT pathway in RGCs, and (2) JAK/STAT pathway mediates RGC survival following 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, P.R. China.No 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

17869246

Citation

Huang, Yao, et al. "JAK/STAT Pathway Mediates Retinal Ganglion Cell Survival After Acute Ocular Hypertension but Not Under Normal Conditions." Experimental Eye Research, vol. 85, no. 5, 2007, pp. 684-95.
Huang Y, Cen LP, Choy KW, et al. JAK/STAT pathway mediates retinal ganglion cell survival after acute ocular hypertension but not under normal conditions. Exp Eye Res. 2007;85(5):684-95.
Huang, Y., Cen, L. P., Choy, K. W., van Rooijen, N., Wang, N., Pang, C. P., & Cui, Q. (2007). JAK/STAT pathway mediates retinal ganglion cell survival after acute ocular hypertension but not under normal conditions. Experimental Eye Research, 85(5), 684-95.
Huang Y, et al. JAK/STAT Pathway Mediates Retinal Ganglion Cell Survival After Acute Ocular Hypertension but Not Under Normal Conditions. Exp Eye Res. 2007;85(5):684-95. PubMed PMID: 17869246.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - JAK/STAT pathway mediates retinal ganglion cell survival after acute ocular hypertension but not under normal conditions. AU - Huang,Yao, AU - Cen,Ling-Ping, AU - Choy,Kwong Wai, AU - van Rooijen,Nico, AU - Wang,Ningli, AU - Pang,Chi Pui, AU - Cui,Qi, Y1 - 2007/08/15/ PY - 2007/04/13/received PY - 2007/06/25/revised PY - 2007/08/01/accepted PY - 2007/9/18/pubmed PY - 2008/2/22/medline PY - 2007/9/18/entrez SP - 684 EP - 95 JF - Experimental eye research JO - Exp Eye Res VL - 85 IS - 5 N2 - Intraocular pressure (IOP) elevation is an important cause of glaucoma. Animal models of ocular hypertension have been widely used to mimic glaucoma to investigate the mechanisms underlying retinal ganglion cell (RGC) death and search for possible cure. The aim of the present study was to examine the role of JAK/STAT pathway in RGC viability in normal condition or after acute IOP elevation. Retinal explants obtained from intact or IOP-elevated eyes were firstly used to examine the effect of the JAK/STAT pathway inhibitors, AG490 and Jak Inhibitor I, on RGC viability in vitro. The role of this signal pathway was further investigated and confirmed in vivo. AG490 and Jak Inhibitor I were applied into the left eye on days 3, 9, and 15 post 2-h IOP elevation at 110mmHg. Fluorescence dye Fluorogold was used to retrogradely label surviving RGCs. Because macrophage recruitment was seen in the IOP-elevated eyes after inhibition of this pathway, clodronate liposomes were used to remove phagocytic cells in the eye and examine the role of JAK/STAT pathway in RGC survival independent of macrophages. Activities and location of JAK/STAT pathway in the retina were examined using Western blotting and immunohistochemistry. We found that inhibition of JAK/STAT pathway did not affect RGC survival in the retinal explants derived from intact eye but caused RGC death in the retinal explants that were derived from IOP-elevated eye. Importantly, the detrimental effect of JAK/STAT pathway inhibition on RGC survival was also observed in vivo following acute IOP elevation, but not in intact eye. In addition, both in vitro and in vivo experiments confirmed a detrimental action of phagocytic cells following acute IOP elevation and the pathway inhibition. Compatible with what were observed in vivo, Western blotting and immunohistochemistry showed that JAK/STAT activities were not present in intact retina, but acute IOP elevation activated JAK/STAT pathway in the retina, in the regions of inner nuclear layer and ganglion cell layer, including RGCs. The IOP elevation-induced JAK/STAT activities were effectively abolished by intravitreal application of AG490. This study thus shows that (1) acute IOP elevation activates JAK/STAT pathway in RGCs, and (2) JAK/STAT pathway mediates RGC survival following IOP elevation but not under normal condition. SN - 0014-4835 UR - https://www.unboundmedicine.com/medline/citation/17869246/JAK/STAT_pathway_mediates_retinal_ganglion_cell_survival_after_acute_ocular_hypertension_but_not_under_normal_conditions_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(07)00228-X DB - PRIME DP - Unbound Medicine ER -