Pakize Nur Akkaya, María Miranda, Inmaculada Almansa, Cigdem Elmas, Dragana Trifunovic, Zohreh Hosseinzadeh, Ayse Sahaboglu
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引用次数: 0
Abstract
The rd2 mouse model, characterized by a mutation in the Prph2 gene, exhibits abnormal development of photoreceptor outer segments, resulting in progressive retinal degeneration. While the correlation between poly-ADP-ribose polymerase (PARP) activity and the degeneration of rod photoreceptors is established in the rd2 model, the specific mechanism driving cone degeneration in this model remains unclear. Furthermore, it is yet to be determined whether inhibiting PARP activity can effectively impede the degeneration of cone photoreceptors in this context. We demonstrated that PARP inhibitors Olaparib, BMN-673, and 3-aminobenzamide (3AB), effectively reduced photoreceptor cell loss in the rd2 retina. Notably, rd2 retinas exhibited decreased cone density, but treatment with PARP inhibitors significantly protected cone photoreceptors. The PARP inhibitors, particularly BMN-673, demonstrated a significant protective effect as evidenced by increased rhodopsin expression within the outer segment and a concurrent decrease in Müller cell activity indicated by GFAP expression. The treatment also resulted in significant changes for markers of oxidative stress, such as glutathione (GSH), and oxidized glutathione (GSSG). Notably, the administration of PARP inhibitors also reduced CD9 expression (extracellular vesicle marker), which were significantly increased within the outer nuclear layer (ONL) in the rd2 retinas. Among PARP inhibitors, BMN-673 demonstrated the highest efficacy in preserving photoreceptors, particularly benefiting cone cells.
期刊介绍:
"Acta Neuropathologica Communications (ANC)" is a peer-reviewed journal that specializes in the rapid publication of research articles focused on the mechanisms underlying neurological diseases. The journal emphasizes the use of molecular, cellular, and morphological techniques applied to experimental or human tissues to investigate the pathogenesis of neurological disorders.
ANC is committed to a fast-track publication process, aiming to publish accepted manuscripts within two months of submission. This expedited timeline is designed to ensure that the latest findings in neuroscience and pathology are disseminated quickly to the scientific community, fostering rapid advancements in the field of neurology and neuroscience. The journal's focus on cutting-edge research and its swift publication schedule make it a valuable resource for researchers, clinicians, and other professionals interested in the study and treatment of neurological conditions.