Abstract
Purpose: :
Age-related cataracts (ARCs) are tightly associated with age and oxidation of the lens. Evidences support the view that the oxidative stress with accumulation of reactive oxygen species (ROS) in the lens is a major factor in inducing ARC. In nuclear and mitochondrial DNA, 8-oxo-7,8-dihydro-2' -deoxyguanosine (8-oxodG) is one of the predominant forms of free radical-induced oxidative lesions, and has therefore been widely used as a biomarker for oxidative stress and risk assessment of degenerative diseases. The 8-oxoguanine DNA glycosylase-1 (OGG1)-initiated base excision repair (BER) pathway operates to remove 8-oxodG lesions. HOGG1 and 8-oxodG have involved in many age-related diseases. However, no study has demonstrated its relationship with ARC. In this study, we investigated the temporal and spatial expression of Hogg1, and studied the correlation of 8-oxodg expression with Hogg1 in ARC.
Methods: :
The anterior lens capsule specimens from 150 human eyes (age 19-80 years) were divided into three groups: group A of young lens (yonger than age 49 without cataract), group B of old but normal lens (older than age 50 without cataract), and group C of ARC lens (older than 50 with ARC). Hogg1 mRNA expression was determined using real-time PCR analysis. Hogg1 protein expression and localization were determined using immunohistochemistry and western blot analysis. 8-OxodG expression was examined by immunohistochemistry.
Results: :
Immunohistochemical 8-oxodG expression was significantly increased in ARC, but decreased in young lens compared with old lens. Accordingly, the expression of Hogg1 was decreased in ARC, and the Hogg1 expression was increased in old lens compared with young ones. A low Hogg1 expression was associated statistically significantly with high 8-oxodG expression in ARC.
Conclusions: :
The negative correlation with 8-oxodG and Hogg1 expression in ARC, indicating that downregulation of Hogg1 likely involves in elevating of 8-oxodG level and play a vicious role in ARC formation.
Keywords: cataract • gene/expression • immunohistochemistry