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Javier Araiz, Roberto Gimeno-Hernández, Ángel Fernández-Carbonell, Francisco Bosch-Morell, Teresa Olivar, Inmaculada Almansa, Maria Miranda; Exogenous thioredoxin attenuates oxidative stress in retinal degeneration but does not modify retinal expression of other growth factors. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5371.
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© ARVO (1962-2015); The Authors (2016-present)
Thioredoxin (TRX) is a well-known and potent antioxidant and antiinflamatory molecule. It is particularly interesting the recent finding of two proteins encoded by the same gene (Rod-derived Cone Viability Factor (RdCVF) and RdCVFL), the first one is involved in the survival of the cones in retinitis pigmentosa (RP) and does not have any thioredoxin effect, but the second one is an active thioredoxin. The purpose of this study was to examine the effect of thioredoxin administration at different time points of the characteristic retinal degeneration observed in the rd1 mice.
Animals were treated in accordance to the ARVO statement for the use of animals in ophthalmic and vision research. TRX-1 (Sigma-Adrich) was administered intraperitoneally (3 MG/KG) to rd1 mice at postnatal day 8 and 14, animals were sacrificed at postnatal days 11 and 17 respectively. In another set of experiments TRX was administered at postnatal days 11, 14, 17, 21 and 25 and sacrificed at postnatal day 28. Retinas were dissected and retinal glutathione and related metabolites were determined by high pressure liquid chromatography (HPLC). Western blot analysis was performed to assess expression of several growth factors (brain-derived neurotrophic factor (BDNF) and vascular endothelial factor (VEGF)), beclin, lysosomal associated membrane protein-2 (LAMP2A) and Atg7.
TRX administration was able to attenuate retinal oxidative stress and regulate thiol metabolism, this change was more important at postnatal day 28 (after 5 doses of TRX). No changes were observed in retinal BDNF and VEGF in both control and rd1 mice after TRX treatment. Beclin, LAMP2A and Atg7 (autophagy markers) expression change in control and rd1 mice with age, but their expression was not affected by TRX treatment in any of the experimental procedures performed.
TRX administration may be an important tool to attenuate oxidative stress in retinal alteration, though further studies are needed to determine the effective dose and pattern of administration.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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