Abstract
Purpose: :
To evaluate changes in three canonical markers for oxidative stress, 4-hydroxy-2-nonenal (HNE), hemeoxygenase-1 (HO-1), and carboxymethyllysine (CML) as a function of normal aging in mice.
Methods: :
Retinas from 1, 6, 12, and 24 month-old male and female C57B/6 mice were analyzed for the presence and distribution of HNE, HO-1, and CML by immunohistochemistry and Western blotting.
Results: :
Our results showed that HNE, a lipoxidation product from the polyunsaturated phospholipids in the cell membrane, was mainly localized in retinal ganglion cell layer, inner nuclear layer, and photoreceptor layer of the retina and the level of HNE was not significantly changed with aging. However, HO-1, an oxidative stress inducible marker, was increased significantly in the mouse retinas in a strict age-dependent manner (Male: 100±12%, 112±15%, 118±16%, 127±16%; Female: 100±13%, 156±22%, 165±18%, 202±22% for 1, 6, 12, and 24 month respectively, p<0.05). Moreover, female mice showed significantly higher level of HO-1 expression in 6, 12, and 24 month-old groups than the same aged male counterparts (Male: 100±12%, 100±13%, 100±12%; Female 128±21%, 133±18%, and 134±17%; P=0.048, P=0.009, p=0.01 respectively). Consistently, CML was increased with age similarly to HO-1 (Male: 100±9%, 104±10%, 107±11%, 122±11%; Female: 100±10%, 139±17%, 156±18%, 182±20% for 1, 6, 12, and 24 month respectively, p<0.05). In addition, 6, 12, and 24 month-old female mice showed higher level of CML compared to male counterpart mice respectively (Male: 100±10%, 100±11%, 100±9%; Female: 119±15%, 131±15%, and 133±15%; P=0.012, P=0.042, p=0.044 respectively).