Thioredoxins 1 and 2 protect retinal ganglion cells from pharmacologically induced oxidative stress, optic nerve transection and ocular hypertension

Yasunari Munemasa, Jacky M.K. Kwong, Seok Hwan Kim, Jae H. Ahn, Joseph Caprioli, Natik Piri

Research output: Chapter in Book/Report/Conference proceedingConference contributionResearchpeer-review

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Abstract

Oxidative damage has been implicated in retinal ganglion cell (RGC) death after optic nerve transection (ONT) and during glaucomatous neuropathy. Here, we analyzed the expression and cell protective role of thioredoxins (TRX), key regulators of the cellular redox state, in RGCs damaged by pharmacologically induced oxidative stress, ONT and elevated intraocular pressure (IOP). The endogenous level of thioredoxin-1 (TRX1) and thioredoxin-2 (TRX2) in RGCs after axotomy and in RGC-5 cells after glutamate/buthionine sulfoximine (BSO) treatment showed upregulation of TRX2, whereas no significant change was observed in TRX1 expression. The increased level TRX-interacting protein (TXNIP) in the retinas was observed 2 and 5 weeks after IOP elevation. TRX1 level was decreased at 2 weeks and more prominently at 5 weeks after IOP increase. No change in TRX2 levels in response to IOP change was observed. Overexpression of TRX1 and TRX2 in RGC-5 treated with glutamate/BSO increased the cell survival by 2- and 3-fold 24 and 48 h after treatment, respectively. Overexpression of these proteins in the retina increased the survival of RGCs by 35 and 135% 7 and 14 days after ONT, respectively. In hypertensive eyes, RGC loss was approximately 27% 5 weeks after IOP elevation compared to control. TRX1 and TRX2 overexpression preserved approximately 45 and 37% of RGCs, respectively, that were destined to die due to IOP increase.

Original languageEnglish
Title of host publicationRetinal Degenerative Diseases
Subtitle of host publicationLaboratory and Therapeutic Investigations
EditorsRobert Anderson, Nawajes Mandal, Joe Hollyfield, Matthew LaVail
Pages355-363
Number of pages9
DOIs
StatePublished - 1 Dec 2010

Publication series

NameAdvances in Experimental Medicine and Biology
Volume664
ISSN (Print)0065-2598

Fingerprint

Optic Nerve Injuries
Ocular Hypertension
Thioredoxins
Oxidative stress
Retinal Ganglion Cells
Optics
Oxidative Stress
Intraocular Pressure
Buthionine Sulfoximine
Retina
Glutamic Acid
Axotomy
Cell death
Oxidation-Reduction

Cite this

Munemasa, Y., Kwong, J. M. K., Kim, S. H., Ahn, J. H., Caprioli, J., & Piri, N. (2010). Thioredoxins 1 and 2 protect retinal ganglion cells from pharmacologically induced oxidative stress, optic nerve transection and ocular hypertension. In R. Anderson, N. Mandal, J. Hollyfield, & M. LaVail (Eds.), Retinal Degenerative Diseases: Laboratory and Therapeutic Investigations (pp. 355-363). (Advances in Experimental Medicine and Biology; Vol. 664). https://doi.org/10.1007/978-1-4419-1399-9_41
Munemasa, Yasunari ; Kwong, Jacky M.K. ; Kim, Seok Hwan ; Ahn, Jae H. ; Caprioli, Joseph ; Piri, Natik. / Thioredoxins 1 and 2 protect retinal ganglion cells from pharmacologically induced oxidative stress, optic nerve transection and ocular hypertension. Retinal Degenerative Diseases: Laboratory and Therapeutic Investigations. editor / Robert Anderson ; Nawajes Mandal ; Joe Hollyfield ; Matthew LaVail. 2010. pp. 355-363 (Advances in Experimental Medicine and Biology).
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abstract = "Oxidative damage has been implicated in retinal ganglion cell (RGC) death after optic nerve transection (ONT) and during glaucomatous neuropathy. Here, we analyzed the expression and cell protective role of thioredoxins (TRX), key regulators of the cellular redox state, in RGCs damaged by pharmacologically induced oxidative stress, ONT and elevated intraocular pressure (IOP). The endogenous level of thioredoxin-1 (TRX1) and thioredoxin-2 (TRX2) in RGCs after axotomy and in RGC-5 cells after glutamate/buthionine sulfoximine (BSO) treatment showed upregulation of TRX2, whereas no significant change was observed in TRX1 expression. The increased level TRX-interacting protein (TXNIP) in the retinas was observed 2 and 5 weeks after IOP elevation. TRX1 level was decreased at 2 weeks and more prominently at 5 weeks after IOP increase. No change in TRX2 levels in response to IOP change was observed. Overexpression of TRX1 and TRX2 in RGC-5 treated with glutamate/BSO increased the cell survival by 2- and 3-fold 24 and 48 h after treatment, respectively. Overexpression of these proteins in the retina increased the survival of RGCs by 35 and 135{\%} 7 and 14 days after ONT, respectively. In hypertensive eyes, RGC loss was approximately 27{\%} 5 weeks after IOP elevation compared to control. TRX1 and TRX2 overexpression preserved approximately 45 and 37{\%} of RGCs, respectively, that were destined to die due to IOP increase.",
author = "Yasunari Munemasa and Kwong, {Jacky M.K.} and Kim, {Seok Hwan} and Ahn, {Jae H.} and Joseph Caprioli and Natik Piri",
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Munemasa, Y, Kwong, JMK, Kim, SH, Ahn, JH, Caprioli, J & Piri, N 2010, Thioredoxins 1 and 2 protect retinal ganglion cells from pharmacologically induced oxidative stress, optic nerve transection and ocular hypertension. in R Anderson, N Mandal, J Hollyfield & M LaVail (eds), Retinal Degenerative Diseases: Laboratory and Therapeutic Investigations. Advances in Experimental Medicine and Biology, vol. 664, pp. 355-363. https://doi.org/10.1007/978-1-4419-1399-9_41

Thioredoxins 1 and 2 protect retinal ganglion cells from pharmacologically induced oxidative stress, optic nerve transection and ocular hypertension. / Munemasa, Yasunari; Kwong, Jacky M.K.; Kim, Seok Hwan; Ahn, Jae H.; Caprioli, Joseph; Piri, Natik.

Retinal Degenerative Diseases: Laboratory and Therapeutic Investigations. ed. / Robert Anderson; Nawajes Mandal; Joe Hollyfield; Matthew LaVail. 2010. p. 355-363 (Advances in Experimental Medicine and Biology; Vol. 664).

Research output: Chapter in Book/Report/Conference proceedingConference contributionResearchpeer-review

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T1 - Thioredoxins 1 and 2 protect retinal ganglion cells from pharmacologically induced oxidative stress, optic nerve transection and ocular hypertension

AU - Munemasa, Yasunari

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N2 - Oxidative damage has been implicated in retinal ganglion cell (RGC) death after optic nerve transection (ONT) and during glaucomatous neuropathy. Here, we analyzed the expression and cell protective role of thioredoxins (TRX), key regulators of the cellular redox state, in RGCs damaged by pharmacologically induced oxidative stress, ONT and elevated intraocular pressure (IOP). The endogenous level of thioredoxin-1 (TRX1) and thioredoxin-2 (TRX2) in RGCs after axotomy and in RGC-5 cells after glutamate/buthionine sulfoximine (BSO) treatment showed upregulation of TRX2, whereas no significant change was observed in TRX1 expression. The increased level TRX-interacting protein (TXNIP) in the retinas was observed 2 and 5 weeks after IOP elevation. TRX1 level was decreased at 2 weeks and more prominently at 5 weeks after IOP increase. No change in TRX2 levels in response to IOP change was observed. Overexpression of TRX1 and TRX2 in RGC-5 treated with glutamate/BSO increased the cell survival by 2- and 3-fold 24 and 48 h after treatment, respectively. Overexpression of these proteins in the retina increased the survival of RGCs by 35 and 135% 7 and 14 days after ONT, respectively. In hypertensive eyes, RGC loss was approximately 27% 5 weeks after IOP elevation compared to control. TRX1 and TRX2 overexpression preserved approximately 45 and 37% of RGCs, respectively, that were destined to die due to IOP increase.

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Munemasa Y, Kwong JMK, Kim SH, Ahn JH, Caprioli J, Piri N. Thioredoxins 1 and 2 protect retinal ganglion cells from pharmacologically induced oxidative stress, optic nerve transection and ocular hypertension. In Anderson R, Mandal N, Hollyfield J, LaVail M, editors, Retinal Degenerative Diseases: Laboratory and Therapeutic Investigations. 2010. p. 355-363. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-1-4419-1399-9_41