Consiglio Nazionale delle Ricerche (CNR) Institute of Neuroscience, Pisa, Italy.
Laboratory of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, Pisa, Italy.
FASEB J. 2019 Sep;33(9):10177-10192. doi: 10.1096/fj.201900414R. Epub 2019 Jun 14.
Hallmark of retinitis pigmentosa (RP) is the primary, genetic degeneration of rods followed by secondary loss of cones, caused by still elusive biologic mechanisms. We previously shown that exposure of rd10 mutant mice, modeling autosomal recessive RP, to environmental enrichment (EE), with enhanced motor, sensorial and social stimuli, results into a sensible delay of retinal degeneration and vision loss. Searching for effectors of EE-mediated retinal protection, we performed transcriptome analysis of the retina of rd10 enriched and control mice and found that gene expression at the peaks of rod and cone degeneration is characterized by a strong inflammatory/immune response, which is however measurably lower in enrichment conditions. Treating rd10 mice with dexamethasone during the period of maximum photoreceptors death lowered retinal inflammation and caused a preservation of cones and cone-mediated vision. Our findings indicate a link between retinal inflammation and bystander cone degeneration, reinforcing the notion that cone vision in RP can be preserved using anti-inflammatory approaches.-Guadagni, V., Biagioni, M., Novelli, E., Aretini, P., Mazzanti, C. M., Strettoi, E. Rescuing cones and daylight vision in retinitis pigmentosa mice.
视网膜色素变性(RP)的特征是 rods 的原发性遗传变性,随后 secondary loss of cones,这是由仍然难以捉摸的生物学机制引起的。我们之前曾表明,对建模常染色体隐性 RP 的 rd10 突变小鼠进行环境富集(EE),增加运动、感官和社交刺激,可导致视网膜变性和视力丧失的明显延迟。为了寻找 EE 介导的视网膜保护的效应物,我们对 rd10 丰富和对照小鼠的视网膜进行了转录组分析,发现 rod 和 cone 变性高峰期的基因表达特征是强烈的炎症/免疫反应,但在富集条件下可测量到的反应较低。在光感受器死亡的高峰期用地塞米松治疗 rd10 小鼠可降低视网膜炎症,并保留 cone 和 cone 介导的视力。我们的发现表明视网膜炎症与旁观者 cone 变性之间存在联系,这强化了使用抗炎方法可以保留 RP 中的 cone 视力的观点。