Purchase this article with an account.
Maria E Marin Castano, Mablo J Marin Carcia, Sergio Recalde, Maria Hernandez, Alfredo Garcia Layana, Retina; Cigarette smoke-related hydroquinone decreases C1q expression through ROS production in the RPE. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4229.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Although the cause of AMD is not fully understood, studies show that oxidative stress and inflammation may play a fundamental role in the etiology of the disease. However, the molecular signal(s) linking oxidation and inflammation to sub-RPE deposit formation is unknown. Demonstration that complement protein C1q may modulate clearance of cell-derived debris following tissue injury and that RPE is likely to play a vital role in cleaning cellular debris may pave the way to unravel the still hidden way(s) linking oxidation to inflammation in AMD. Our long term objective is to understand the mechanism(s) by which sub-lethal pathological changes initiated in the RPE by chronic oxidative stress promote insufficient clearance of RPE-derived debris, which will lead to the formation and accumulation of sub-RPE deposits.
Mice were divided into 2 group. Animals were exposed to drinking water (Group 1) or to hydroquinone (HQ) in drinking (Group 2) for 4 weeks. At the end of the experimental period, RPE sheets were isolated and mRNA and protein extracted in lysis buffer and quantified. ROS production was determined in supernatants form fresh RPE sheets by means of the oxidationsensitive fluorescent probe dye, H2DCFDA. Production of (O2-), was determined by using dihydroethidium (DHE). ROS levels were expressed as mean fluorescence intensity. C1q expression was determined by real-time PCR and Western blot analysis.<br /> <br /> In parallel, isolated RPE sheets from control mice were exposed for one hour to the selective NADPH oxidase inhibitor ML171 50 nM, to the general ROS scavenger N-acetyl-L-cysteine (NAC) 100 microM, or combination of both prior to HQ 100 microM exposure for 8 hrs. At the end of the treatment, ROS production and C1q expression were determined as mentioned above.
Mice exposed to HQ displayed a significant increase in ROS production and a significant decrease in C1q expression in the RPE. Moreover, RPE sheets incubated with HQ also presented a significant increase in ROS production and decrease in C1q expression. These effects were inhibited by the combination of NAC and ML171.
The decrease in C1q may promote insufficient clearance of RPE-derived debris, which will lead to the formation of sub-RPE deposits.
This PDF is available to Subscribers Only