Altered mRNA Expression of 'Ahr-Nrf2 Gene Batteries' in the Retinas of Senescence-Accelerated OXYS Rats during Development of AMDLike Retinopathy

Abstract

Background: Etiology of age-related macular degeneration (AMD) is poorly understood, although oxidative stress and environmental risk factors have been implicated. Recently, AhR (arylhydrocarbon receptor) and Nrf2 (nuclear factor erythroid 2-related factor 2) were considered as AMD candidate genes. Transcription products of the AhR-Nrf2 “gene battery” are important in mediating cellular response to oxidative stress. The animal model for AMD (senescence accelerated OXYS rats) was used. Ophthalmoscopy revealed no pathologic changes in OXYS rats’ retinas at the age of 1 month; however, at the age of 3 months, the first signs of retinopathy were recorded in the eyes of all animals tested. The aim of the present study was to determine whether the balance between prooxidizing (AhR-dependent) and antioxidant (Nrf2-dependent) systems plays a crucial role in the onset and/or progression of age-related retinopathy. Methods: In the retina of 1-, 3- and 12- month-old OXYS and Wistar rats mRNA levels of CYP1A1, CYP1A2, CYP1B1, GSTA1, NQO1, ALDH3A1, UGT1A6, UGT1A9, AhR and Nrf2 genes were measured by qRT-PCR. Results: In the retinas of 1-month OXYS rats, the mRNA level of only AhR was reduced when compared with Wistar rats. At the age of 3 months, a decline in the mRNA levels was detected for CYP1A and CYP1A2, but not for CYP1B1 in OXYS rats. mRNA levels of Nrf2, were higher in OXYS rats when compared with Wistar rats. Levels of the genes that are regulated by AhR and Nrf2 (NQO1 and UGT1A6), were reduced when compared with Wistar rats, and GSTA1: mRNA level was increased. Conclusions: The data obtained allow us to conclude that the AhR-Nrf2 “gene battery” may be involved in the pathogenesis of retinopathy in the OXYS rats. One of the triggers for the starting of oxidative stress during the progression of retinopathy may be the inborn reduced level of AhR expression.