Altered Pannexin2 Expression in Retinal Degeneration: Insights from the P23H Mouse Model of Retinis Pigmentosa

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Abstract
Pannexins are large channels involved in purinergic signaling within the nervous system. However, their role in human disease and their therapeutic potential remain poorly understood, particularly for Pannexin-2 (Panx2). The aim of this study was to investigate whether Panx2 is associated with retinal neurodegenerative diseases. Using immunohistochemistry and flow cytometry, we analyzed Panx2 expression in the retina of the P23H mouse model of retinitis pigmentosa and in control C57BL/6J mice. We observed that healthy retinas contained a small population of Panx2-positive cells. In contrast, the Panx2 positive population was increased in the retinas of P23H retina, particulary at advanced stages of the disease. Panx2 was found to co-occur with the purinergic receptors P2X7R but not with P2X4R. This result was further supported by the reanalysis of RNA-seq data from GEO functional genomics data repository, which indicated an increased Panx2 mRNA expression in P23H mice at intermediate stages of the disease, compared with control animals. Together, these findings suggest that Panx2 expression is altered during retinal degeneration in the P23H model and may be associated with purinergic signaling pathways involved in disease progression. These results raise interesting questions for further investigation regarding the role of Panx2 in retinal degeneration. Graphical Abstract Schematic representation of the study design, highlighting the key findings using the P23H mouse model of retinitis pigmentosa
Funding Information
  • Horizon 2020 (HORIZON MSCA 2021-DN-01-01_RETORNA 101073316)
  • Universidad de Alicante (UAFPU23-04)
  • Universidad de Alicante (REDSALUD25-03)

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