Glutathione-dependent formaldehyde dehydrogenase (ADH3) and low km mitochondrial aldehyde dehydrogenase (ALDH2). New evidence for differential expression in the rat retina in response to oxidative stress

Abstract

Objectives: Epidemiological and experimental studies support the involvement of lipid peroxidation (LPO) in retinal diseases. In addition to other pathogenic mechanisms not fully understood, the possibility remains that peroxidic aldehydes, acting as cytotoxic chemicals, mediate in the progression of chronic ocular disorders. Methods: To test proper mechanisms involved in removing peroxidic aldehydes from the retina, in an attempt to understand long-lasting changes induced by LPO, the oxidative and antioxidant enzymatic activities, as well as the retinal distribution and activity of glutathione-dependent formaldehyde dehydrogenase (ADH3) and low km mitochondrial aldehyde dehydrogenase (ALDH2), were studied and compared with induced LPO sites in the adult rat retina. Biochemical enzymatic-colorimetric assays, histochemical and immunocytochemical analyses were carried out in the mature rat retinal tissues. Statistics were performed by the SPSS 15.0 program. Results: Data revealed (1) the noticeable LPO and glutathione (GSH) enzymatic system retinal and optic nerve activities; (2) the retinal expression and distribution of both the ADH3 and ALDH2; and (3) the co-localisation of iron/nicotine adenine dinucleotide phosphate (Fe/NADPH)-induced LPO, mainly in the outermost and innermost retinal strata, as compared to the rest of the retinal layers (p < 0.001). Conclusions: Changes in the GSH and GSH enzymatic system, and in the ADH3 and ALDH2 retinal expression and distribution might be crucial in assessing the intrinsic mechanisms of LPO-mediated retinopathies. Further research is needed to evaluate these findings and their application to new ophthalmological therapy.