Tags

Type your tag names separated by a space and hit enter

Overexpression of thioredoxins 1 and 2 increases retinal ganglion cell survival after pharmacologically induced oxidative stress, optic nerve transection, and in experimental glaucoma.
Trans Am Ophthalmol Soc. 2009 Dec; 107:161-5.TA

Abstract

PURPOSE

Oxidative damage is implicated in retinal ganglion cell (RGC) death after optic nerve transection (ONT) and in glaucoma. We analyzed the expression and protective effects of thioredoxins (TRXs), regulators of the cellular reduction-oxidative (redox) state, in RGCs damaged by pharmacologically induced oxidative stress, ONT, and elevated intraocular pressure (IOP).

METHODS

ONT and glaucoma models in the rat were used. The glaucoma model was generated in albino rats by intracameral injection of india ink followed by ab externo laser applications to the pigmented trabecular band. Retrograde labeling of RGCs was performed with dextran tetramethylrhodamine. RGC isolation from rat retinas was performed with magnetic beads coated with Thy-1 monoclonal antibody. Immunoblot analysis, RGC-5 culture and transfection, and cell viability assays were used. Gene delivery was performed with in vivo electroporation.

RESULTS

Endogenous levels of thioredoxin-2 (TRX2) in RGCs after axotomy and in RGC-5 cells after glutamate/buthionine sulfoximine (BSO) treatment were up-regulated. An increased level of TRX-interacting protein (TXNIP) in the retina was observed 2 and 5 weeks after IOP elevation. TRX1 levels were decreased at 2 weeks and more prominently at 5 weeks after IOP elevation. No change in TRX2 levels in response to IOP elevation was detected. Overexpression of TRX1 and TRX2 in RGC-5 treated with glutamate/BSO increased the cell survival by twofold and threefold 24 and 48 hours after treatment, respectively. Overexpression of these proteins in the retina in vivo increased the survival of RGCs by 35% and 135% at 7 and 14 days after ONT, respectively. In hypertensive eyes, RGC loss was approximately 27% after 5 weeks of IOP elevation compared to controls. TRX1 and TRX2 overexpression preserved approximately 45% and 37% of RGCs, respectively, in the glaucoma model compared to controls.

CONCLUSION

Thioredoxin overexpression protects RGCs from death after optic nerve axotomy, in pharmacologically induced oxidative stress in vitro and in an animal model of glaucoma.

Authors+Show Affiliations

Jules Stein Eye Institute, University of California, Los Angeles, USA.No 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

20126492

Citation

Caprioli, Joseph, et al. "Overexpression of Thioredoxins 1 and 2 Increases Retinal Ganglion Cell Survival After Pharmacologically Induced Oxidative Stress, Optic Nerve Transection, and in Experimental Glaucoma." Transactions of the American Ophthalmological Society, vol. 107, 2009, pp. 161-5.
Caprioli J, Munemasa Y, Kwong JM, et al. Overexpression of thioredoxins 1 and 2 increases retinal ganglion cell survival after pharmacologically induced oxidative stress, optic nerve transection, and in experimental glaucoma. Trans Am Ophthalmol Soc. 2009;107:161-5.
Caprioli, J., Munemasa, Y., Kwong, J. M., & Piri, N. (2009). Overexpression of thioredoxins 1 and 2 increases retinal ganglion cell survival after pharmacologically induced oxidative stress, optic nerve transection, and in experimental glaucoma. Transactions of the American Ophthalmological Society, 107, 161-5.
Caprioli J, et al. Overexpression of Thioredoxins 1 and 2 Increases Retinal Ganglion Cell Survival After Pharmacologically Induced Oxidative Stress, Optic Nerve Transection, and in Experimental Glaucoma. Trans Am Ophthalmol Soc. 2009;107:161-5. PubMed PMID: 20126492.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpression of thioredoxins 1 and 2 increases retinal ganglion cell survival after pharmacologically induced oxidative stress, optic nerve transection, and in experimental glaucoma. AU - Caprioli,Joseph, AU - Munemasa,Yasunari, AU - Kwong,Jacky M K, AU - Piri,Natik, PY - 2010/2/4/entrez PY - 2010/2/4/pubmed PY - 2010/5/11/medline SP - 161 EP - 5 JF - Transactions of the American Ophthalmological Society JO - Trans Am Ophthalmol Soc VL - 107 N2 - PURPOSE: Oxidative damage is implicated in retinal ganglion cell (RGC) death after optic nerve transection (ONT) and in glaucoma. We analyzed the expression and protective effects of thioredoxins (TRXs), regulators of the cellular reduction-oxidative (redox) state, in RGCs damaged by pharmacologically induced oxidative stress, ONT, and elevated intraocular pressure (IOP). METHODS: ONT and glaucoma models in the rat were used. The glaucoma model was generated in albino rats by intracameral injection of india ink followed by ab externo laser applications to the pigmented trabecular band. Retrograde labeling of RGCs was performed with dextran tetramethylrhodamine. RGC isolation from rat retinas was performed with magnetic beads coated with Thy-1 monoclonal antibody. Immunoblot analysis, RGC-5 culture and transfection, and cell viability assays were used. Gene delivery was performed with in vivo electroporation. RESULTS: Endogenous levels of thioredoxin-2 (TRX2) in RGCs after axotomy and in RGC-5 cells after glutamate/buthionine sulfoximine (BSO) treatment were up-regulated. An increased level of TRX-interacting protein (TXNIP) in the retina was observed 2 and 5 weeks after IOP elevation. TRX1 levels were decreased at 2 weeks and more prominently at 5 weeks after IOP elevation. No change in TRX2 levels in response to IOP elevation was detected. Overexpression of TRX1 and TRX2 in RGC-5 treated with glutamate/BSO increased the cell survival by twofold and threefold 24 and 48 hours after treatment, respectively. Overexpression of these proteins in the retina in vivo increased the survival of RGCs by 35% and 135% at 7 and 14 days after ONT, respectively. In hypertensive eyes, RGC loss was approximately 27% after 5 weeks of IOP elevation compared to controls. TRX1 and TRX2 overexpression preserved approximately 45% and 37% of RGCs, respectively, in the glaucoma model compared to controls. CONCLUSION: Thioredoxin overexpression protects RGCs from death after optic nerve axotomy, in pharmacologically induced oxidative stress in vitro and in an animal model of glaucoma. SN - 1545-6110 UR - https://www.unboundmedicine.com/medline/citation/20126492/Overexpression_of_thioredoxins_1_and_2_increases_retinal_ganglion_cell_survival_after_pharmacologically_induced_oxidative_stress_optic_nerve_transection_and_in_experimental_glaucoma_ L2 - https://aosonline.org/assets/xactions/2009/1545-6110_v107_p161.pdf DB - PRIME DP - Unbound Medicine ER -