The hereditary disease Retinitis pigmentosa results in severe vision loss due to photoreceptor degeneration by unclear mechanisms. In several disease models, the second messenger cGMP accumulates in the degenerating photoreceptors, where it may over-activate specific cGMP-interacting proteins, like cGMP-dependent protein kinase. Moreover, interventions that counteract the activity of these proteins lead to reduced photoreceptor cell death. Yet there is little or no information whether other than such regular cGMP-interactors are present in the retina, which we, therefore, investigated in wild-type and retinal degeneration (rd1, rd10, and rd2) mouse models. An affinity chromatography based proteomics approach that utilized immobilized cGMP analogs was applied to enrich and select for regular and potentially new cGMP-interacting proteins as identified by mass spectrometry. This approach revealed 12 regular and 10 potentially new retinal cGMP-interacting proteins (e.g., EPAC2 and CaMKIIα). Several of the latter were found to be expressed in the photoreceptors and to have proximity to cGMP and may thus be of interest when defining prospective therapeutic targets or biomarkers for retinal degeneration.

中文翻译：

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正常和退化小鼠神经视网膜中的 cGMP 系统：通过蛋白质组学方法鉴定的具有 cGMP 相互作用潜力的新蛋白质

遗传性疾病视网膜色素变性导致光感受器变性通过不明机制导致严重视力丧失。在几种疾病模型中，第二信使 cGMP 在退化的光感受器中积累，在那里它可能过度激活特定的 cGMP 相互作用蛋白，如 cGMP 依赖性蛋白激酶。此外，抵消这些蛋白质活性的干预措施会导致光感受器细胞死亡减少。然而，除了这种规则的 cGMP 相互作用物之外，视网膜中是否存在很少或根本没有信息，因此我们在野生型和视网膜变性（rd1、rd10和rd2) 小鼠模型。使用固定化 cGMP 类似物的基于亲和层析的蛋白质组学方法被应用于富集和选择常规和潜在的新 cGMP 相互作用蛋白，如质谱法所鉴定的。这种方法揭示了 12 种常规和 10 种潜在的新视网膜 cGMP 相互作用蛋白（例如，EPAC2 和 CaMKII α）。发现后者中的一些在光感受器中表达并与 cGMP 接近，因此在定义视网膜变性的预期治疗靶点或生物标志物时可能会引起关注。