Abstract
Purpose::
Oxidative retinal vascular damage has been demonstrated to significantly contribute to several eye diseases including diabetic retinopathy (DR) and age-related macula degeneration (AMD). Aging and diabetes can accelerate oxidant production in the retina, however decreased anti-oxidative capacity may also contribute to oxidative damage. The thioredoxin system (TRXS) is a powerful and tightly regulated anti-oxidant system which is ubiquitously expressed and which exerts important cellular functions such as survival and gene expression. To determine whether alterations in the TRXS could potentially contribute to retinal oxidative damage we performed experiments assessing the expression levels of different components of the TRXS in retinas of aged or diabetic rats.
Methods::
The expression levels of thioredoxin-1 (TRX-1) and its negative regulator, thioredoxin binding protein (TXNIP-1) were assessed, by Western blotting and immunohistochemical analyses, in 3 or 12 months old rat retinas and compared to retinas of streptozotocin-induced diabetic rats at different times of hyperglycemia (2, 4 weeks).
Results::
Immunohistochemical analysis showed that TRX-1 and TXNIP-1 were predominantly localized around the retinal blood vessels in each of the animal groups. Western blotting and immunohistochemical analyses also showed that hyperglycemia stimulated a time-dependent (4 weeks>2weeks>control normoglycemic) increase in both TRX-1 and, in particular, TXNIP protein expression. Finally, TRX-1 and TXNIP-1 expression were also found increased in the retinas of 12 months old rats as compared to retinas of 3 months old rats.
Conclusions::
In conclusion, oxidative stress in the aged and in the diabetic retina is associated with alteration in the thioredoxin system as shown by increased expression of TRX-1 and its inhibitory partner TXNIP-1.
Keywords: aging • diabetes • oxidation/oxidative or free radical damage