Purinergic Receptors P2X7 and P2X4 as Markers of Disease Progression in the rd10 Mouse Model of Inherited Retinal Dystrophy

Abstract

The purinergic receptor P2X7 (P2X7R) is implicated in all neurodegenerative diseases of the central nervous system. It is also involved in the retinal degeneration associated with glaucoma, age-related macular degeneration, and diabetic retinopathy, and its overexpression in the retina is evident in these disorders. Retinitis pigmentosa is a progressive degenerative disease that ultimately leads to blindness. Here, we investigated the expression of P2X7R during disease progression in the rd10 mouse model of RP. As the purinergic receptor P2X4 is widely co-expressed with P2X7R, we also studied its expression in the retina of rd10 mice. The expression of P2X7R and P2X4R was examined by immunohistochemistry, flow cytometry, and western blotting. In addition, we analyzed retinal functionality by electroretinographic recordings of visual responses and optomotor tests and retinal morphology. We found that the expression of P2X7R and P2X4R increased in rd10 mice concomitant with disease progression, but with different cellular localization. Our findings suggest that P2X7R and P2X4R might play an important role in RP progression, which should be further analyzed for the pharmacological treatment of inherited retinal dystrophies.

P2X7R and P2X4R expression of mice submandibular gland in high-fat diet/streptozotocin-induced type 2 diabetes

“…In addition, several studies have investigated purinergic receptors in various organs affected by T2DM, including the retina, nephrons, microglia, neurons, and gastrointestinal organs 40 , 41 . No evidence has been found regarding inflammatory purinergic receptors in the SG after the development of T2DM.…”

“…6 a–l). There is some evidence suggesting the coexpression of P2X7R and P2X4R, although the precise interaction between them remains unknown 40 . A positive interaction between these receptors has been reported 42 , which may explain the corresponding patterns of P2X7R and P2X7R distribution.…”

“…We observed reduced P2X7 receptor expression in the CON11w and CON13w groups. Generally, P2X7R participates in the initial stages of inflammation, and its expression increases in response to macrophages, further aggravating inflammation 43 – 45 . A previous study on the retina also reported that P2X7R and P2X4R are associated with the progression of diabetic retinopathy 43 which is related to our results suggested that the expression of P2X7 receptors was distinctly observed in the DM11w group and became more intense in the DM13w group.…”

“…Generally, P2X7R participates in the initial stages of inflammation, and its expression increases in response to macrophages, further aggravating inflammation 43 – 45 . A previous study on the retina also reported that P2X7R and P2X4R are associated with the progression of diabetic retinopathy 43 which is related to our results suggested that the expression of P2X7 receptors was distinctly observed in the DM11w group and became more intense in the DM13w group. The significantly higher expression of P2X7R and P2X4R in T2DM could be explained by the response of purinergic receptors to a stressful environment.…”

Hyperreflective Band in the Ganglion Cell Layer in Retinitis Pigmentosa

“…32 Strikingly, expression of P2X7R and P2X4R (another purinergic receptor involved in neurodegeneration) 33 is upregulated in a different rodent model of RP, the rd10 mouse. 34 3) In the P23H rat model, the onset of RP and related gliosis can also be dramatically accelerated by eliciting a mild chronic inflammation through systemic injection of lipopolysaccharides (LS); remarkably, the gliosis induced by LS is mainly of the Müller cell type, and affects several retinal layers with a mild thickening of the GCL. 35 LPS possibly acts through an entirely different pathogenic pathway, that is, microglial activation through Toll-like receptor 4 (TLR4), which triggers the production and release of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), by the mitogen-activated protein kinase (MAPK) and nuclear factor kappa beta (NF-kβ) routes.…”