Thioredoxins 1 and 2 protect retinal ganglion cells from pharmacologically induced oxidative stress, optic nerve transection and ocular hypertension.
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.
Munemasa
Yasunari
Y
Jules Stein Eye Institute, UCLA, Los Angeles, CA 90095, USA.
Kwong
Jacky M K
JM
Kim
Seok H
SH
Ahn
Jae H
JH
Caprioli
Joseph
J
Piri
Natik
N
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002470:Cell Survival; D019610:Cytoprotection; D007429:Intraocular Pressure / Q000502:physiology; D008297:Male; D009798:Ocular Hypertension / Q000150:complications* / Q000503:physiopathology / Q000517:prevention & control; D020221:Optic Nerve Injuries / Q000150:complications* / Q000503:physiopathology / Q000517:prevention & control; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000473:pathology*; D013879:Thioredoxins / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C493796:TXNIP protein, rat; D013879:Thioredoxins