Nucleoredoxin Plays a Key Role in the Maintenance of Retinal Pigmented Epithelium Differentiation

MARIANA I. HOLUBIEC 1,2,* , JUAN I. ROMERO 3, CLAUDIA URBAINSKY 4 , MANUELA GELLERT 4, PABLO GALEANO 3 , FRANCISCO CAPANI , CHRISTOPHER HORST LILLIG 4 AND EVA-MARIA HANSCHMANN 4,

Antioxidants

MDP!

Año: 2022

2076-3921

Nucleoredoxin (Nrx) belongs to the Thioredoxin protein family and functions in redoxmediatedsignal transduction. It contains the dithiol active site motif Cys-Pro-Pro-Cys and interactsand regulates different proteins in distinct cellular pathways. Nrx was shown to be catalytically activein the insulin assay and recent findings indicate that Nrx functions, in fact, as oxidase. Here, wehave analyzed Nrx in the mammalian retina exposed to (perinatal) hypoxia-ischemia/reoxygenation,combining ex vivo and in vitro models. Our data show that Nrx regulates cell differentiation, whichis important to (i) increase the number of glial cells and (ii) replenish neurons that are lost followingthe hypoxic insult. Nrx is essential to maintain cell morphology. These regulatory changes arerelated to VEGF but do not seem to be linked to the Wnt/-catenin pathway, which is not affected byNrx knock-down. In conclusion, our results strongly suggest that hypoxia-ischemia could lead toalterations in the organization of the retina, related to changes in RPE cell differentiation. Nrx mayplay an essential role in the maintenance of the RPE cell differentiation state via the regulation ofVEGF release.