Departamento de Fisiología, Genética y Microbiología, Universidad de Alicante, 03690 Alicante, Spain.
Departamento de Óptica, Farmacología y Anatomía, Universidad de Alicante, 03690 Alicante, Spain.
Int J Mol Sci. 2022 Nov 25;23(23):14758. doi: 10.3390/ijms232314758.
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.
嘌呤能受体 P2X7(P2X7R)与中枢神经系统的所有神经退行性疾病都有关。它也与青光眼、年龄相关性黄斑变性和糖尿病性视网膜病变相关的视网膜变性有关,其在这些疾病中的过度表达在视网膜中是明显的。色素性视网膜炎是一种进行性退行性疾病,最终导致失明。在这里,我们研究了嘌呤能受体 P2X4 与 P2X7R 广泛共表达的情况下,P2X7R 在 rd10 小鼠色素性视网膜炎模型疾病进展过程中的表达。我们通过免疫组织化学、流式细胞术和 Western blot 分析了 P2X7R 和 P2X4R 的表达。此外,我们通过视觉反应和光动测试的视网膜电图记录以及视网膜形态学分析来分析视网膜功能。我们发现,P2X7R 和 P2X4R 的表达随着疾病的进展在 rd10 小鼠中增加,但细胞定位不同。我们的研究结果表明,P2X7R 和 P2X4R 可能在 RP 进展中发挥重要作用,这应该进一步分析用于遗传性视网膜营养不良的药物治疗。