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Changes in ocular aquaporin-4 (AQP4) expression following retinal injury.
Mol Vis. 2008 Sep 25; 14:1770-83.MV

Abstract

PURPOSE

Changes in the expression of water channels or aquaporins (AQP) have been reported in several diseases. However, such changes and mechanisms remain to be evaluated for retinal injury. This study was designed to analyze changes in the expression of AQP4 following elevation of intraocular pressure (IOP) and after intravitreal endothelin-1 injection and the potential involvement of the ubiquitin-dependent proteasome.

METHODS

Retinal injuries were induced by the elevation of intraocular pressure in rat eyes using the Morrison model or following endothelin-1 intravitreal injection. Immunohistochemistry using a combination of glial fibrillary acidic protein (GFAP) and aquaporin-4 antibodies were employed to follow changes in the optic nerve head astrocytes. Real-time quantitative PCR (Q-PCR) was used for measuring changes in AQP4, ubiquitin hydrolase L1 (UCH-L1), and beta-actin messages. Changes in AQP4, caspase-3, thy-1, ubiquitination, and GFAP expression were also followed in total retinal extracts using western blotting. An S5a column was used to purify ubiquitinated proteins.

RESULTS

In retinas of both injury models, there was an upregulation of GFAP (a marker of astrogliosis), caspase-3, and downregulation of thy-1, a marker for retinal ganglion cell stress, and decreased retinal AQP4 mRNA and protein levels as determined by Q-PCR, and western blotting, respectively. By contrast, IOP enhanced expression and co-localization of GFAP and AQP4 in optic nerve astrocytes. AQP4 was detected in affinity-purified ubiquitinated proteins using S5a column, suggesting that AQP4 is a target for degradation by the ubiquitin-dependent proteasome. While elevation of IOP induced an increase in ubiquitination in retinal extracts, it decreased ubiquitination in optic nerve extracts as detected by western blotting. Enhanced ubiquitination and decreased ubiquitination appear to correlate with AQP4 expression. IOP decreased UCH-L1 (or protein gene protein [PGP9.5]) in retinal extracts as judged by Q-PCR.

CONCLUSIONS

The enhanced expression of AQP4 in optic nerve astrocytes following elevation of IOP may explain the astrocytic hypertrophy normally seen in glaucoma patients and may involve alteration in the activity of ubiquitin-dependent proteasomal degradation system. The decreased ubiquitination in the optic nerve may lead to increased levels of proapoptotic proteins known to be degraded by the proteasome, and thus to axonal degeneration in glaucoma.

Authors+Show Affiliations

Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, TX, USA. adibas@hsc.unt.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18836575

Citation

Dibas, Adnan, et al. "Changes in Ocular Aquaporin-4 (AQP4) Expression Following Retinal Injury." Molecular Vision, vol. 14, 2008, pp. 1770-83.
Dibas A, Yang MH, He S, et al. Changes in ocular aquaporin-4 (AQP4) expression following retinal injury. Mol Vis. 2008;14:1770-83.
Dibas, A., Yang, M. H., He, S., Bobich, J., & Yorio, T. (2008). Changes in ocular aquaporin-4 (AQP4) expression following retinal injury. Molecular Vision, 14, 1770-83.
Dibas A, et al. Changes in Ocular Aquaporin-4 (AQP4) Expression Following Retinal Injury. Mol Vis. 2008 Sep 25;14:1770-83. PubMed PMID: 18836575.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in ocular aquaporin-4 (AQP4) expression following retinal injury. AU - Dibas,Adnan, AU - Yang,Ming-Hui, AU - He,Shaoqing, AU - Bobich,Joseph, AU - Yorio,Thomas, Y1 - 2008/09/25/ PY - 2008/03/11/received PY - 2008/08/20/accepted PY - 2008/10/7/pubmed PY - 2008/11/15/medline PY - 2008/10/7/entrez SP - 1770 EP - 83 JF - Molecular vision JO - Mol Vis VL - 14 N2 - PURPOSE: Changes in the expression of water channels or aquaporins (AQP) have been reported in several diseases. However, such changes and mechanisms remain to be evaluated for retinal injury. This study was designed to analyze changes in the expression of AQP4 following elevation of intraocular pressure (IOP) and after intravitreal endothelin-1 injection and the potential involvement of the ubiquitin-dependent proteasome. METHODS: Retinal injuries were induced by the elevation of intraocular pressure in rat eyes using the Morrison model or following endothelin-1 intravitreal injection. Immunohistochemistry using a combination of glial fibrillary acidic protein (GFAP) and aquaporin-4 antibodies were employed to follow changes in the optic nerve head astrocytes. Real-time quantitative PCR (Q-PCR) was used for measuring changes in AQP4, ubiquitin hydrolase L1 (UCH-L1), and beta-actin messages. Changes in AQP4, caspase-3, thy-1, ubiquitination, and GFAP expression were also followed in total retinal extracts using western blotting. An S5a column was used to purify ubiquitinated proteins. RESULTS: In retinas of both injury models, there was an upregulation of GFAP (a marker of astrogliosis), caspase-3, and downregulation of thy-1, a marker for retinal ganglion cell stress, and decreased retinal AQP4 mRNA and protein levels as determined by Q-PCR, and western blotting, respectively. By contrast, IOP enhanced expression and co-localization of GFAP and AQP4 in optic nerve astrocytes. AQP4 was detected in affinity-purified ubiquitinated proteins using S5a column, suggesting that AQP4 is a target for degradation by the ubiquitin-dependent proteasome. While elevation of IOP induced an increase in ubiquitination in retinal extracts, it decreased ubiquitination in optic nerve extracts as detected by western blotting. Enhanced ubiquitination and decreased ubiquitination appear to correlate with AQP4 expression. IOP decreased UCH-L1 (or protein gene protein [PGP9.5]) in retinal extracts as judged by Q-PCR. CONCLUSIONS: The enhanced expression of AQP4 in optic nerve astrocytes following elevation of IOP may explain the astrocytic hypertrophy normally seen in glaucoma patients and may involve alteration in the activity of ubiquitin-dependent proteasomal degradation system. The decreased ubiquitination in the optic nerve may lead to increased levels of proapoptotic proteins known to be degraded by the proteasome, and thus to axonal degeneration in glaucoma. SN - 1090-0535 UR - https://www.unboundmedicine.com/medline/citation/18836575/Changes_in_ocular_aquaporin_4__AQP4__expression_following_retinal_injury_ DB - PRIME DP - Unbound Medicine ER -