TRX, a small, ubiquitous protein (molecular weight, 13,000), with two redox-active half-cystine residues, -Cys-Gly-Pro-Cys-, in its active center, functions as an activator of the transcription factor and a regulator of the intracellular apoptotic pathway.
33 34 Thus, TRX is a major endogenous redox regulator. It is upregulated in the retinal tissue in response to retinal ischemia–reperfusion injury.
11 and intravenous injection of recombinant TRX inhibits retinal ischemia–reperfusion injury.
17 Accordingly, TRX is an endogenous protector against oxidative stress in the retina. In the present study, TRX was upregulated in the outer retinal segment in response to light exposure
(Fig. 1) , indicating that TRX also has a role against light-induced photoreceptor cell damage. GRX is a member of the TRX superfamily and also a redox-active protein that contains a conserved redox-active center.
35 In our results, GRX was not affected by light exposure, suggesting a specific role of TRX among the endogenous redox regulators in the retinal response to photooxidative stress. GSH, a cysteine-containing tripeptide (γ-glutamyl-cysteinyl-glycine), is also one of the major endogenous thiol antioxidants as well as TRX. In our results, retinal GSH levels decreased in response to light exposure in PBS-treated mice
(Fig. 2) . Because GSH tissue levels decrease in response to various types of oxidative stress,
36 37 our results suggest that intense light causes oxidative stress on the retina and that GSH has a protective role against light-induced retinal damage. The alteration of GSH tissue levels seems to be correlated with the change in the HNE-modified protein or the 8-OHdG index. These results suggest a close association between oxidative stress and alteration of redox status. Because TRX and GSH are major regulators of the tissue redox environment, increases or decreases of these molecules suggest possible alterations in redox status during retinal photooxidative stress. Moreover, NAC administration preserved GSH tissue levels
(Fig. 2) and suppressed upregulation of TRX
(Fig. 1) . These results suggest that exogenous thiol replenishment with NAC partially modulates tissue redox status through modulation of endogenous TRX and GSH levels and reduces the oxidative stress resulting from light exposure.