Cantó Antolín, Martínez-González Javier, Almansa Inmaculada, López-Pedrajas Rosa, Hernández-Rabaza Vicente, Olivar Teresa, Miranda María
Department of Biomedical Sciences, Faculty of Health Sciences, Institute of Biomedical Sciences, Cardenal Herrera-CEU University, CEU Universities, 46115 Valencia, Spain.
Antioxidants (Basel). 2022 Sep 29;11(10):1950. doi: 10.3390/antiox11101950.
(1) Background: Retinitis pigmentosa (RP) is characterized by progressive photoreceptor death. A Prph2Rd2 or an rds mouse is an RP model that closely reflects human RP. The objective of this study was to investigate the relationship of rod and cone death with oxidative stress and inflammation in rds mice. (2) Methods: The retinas of control and rds mice on postnatal days (PN) 11, 17, 21, 28, 35, and 42 were used. Oxidative damage to macromolecules, glutathione (GSH and GSSG), GSH synthesis enzymes, glial fibrillar acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba1), and cluster of differentiation 68 (CD68) was studied. (3) Results: The time sequence of oxidative stress and inflammation changes in rds mice occurs as follows: (i) At PN11, there is a small increase in photoreceptor death and in the microglial cells; (ii) at PN17, damage to the macromolecules is observed; (iii) at PN21, the maximum photoreceptor death rate is detected and there is an increase in GSH-GSSG and GFAP; (iv) at PN21, the microglial cells are activated; and(v) at PN28, there is a decrease in GSH synthesis enzymes. (4) Conclusions: These findings contribute to the understanding of RP physiopathology and help us to understand whether oxidative stress and inflammation are therapeutic targets. These findings contribute to our understanding that, in RP, oxidative stress and inflammation evolution and their relationship are time-dependent. In this sense, it is important to highlight that both processes are potential therapeutic targets in this disease.
（1）背景：视网膜色素变性（RP）的特征是光感受器进行性死亡。Prph2Rd2或rds小鼠是一种能密切反映人类RP的RP模型。本研究的目的是探讨rds小鼠视杆和视锥细胞死亡与氧化应激和炎症之间的关系。（2）方法：使用出生后第11、17、21、28、35和42天的对照小鼠和rds小鼠的视网膜。研究了大分子的氧化损伤、谷胱甘肽（GSH和GSSG）、GSH合成酶、胶质纤维酸性蛋白（GFAP）、离子钙结合衔接分子1（Iba1）和分化簇68（CD68）。（3）结果：rds小鼠氧化应激和炎症变化的时间顺序如下：（i）在出生后第11天，光感受器死亡和小胶质细胞略有增加；（ii）在出生后第17天，观察到大分子损伤；（iii）在出生后第21天，检测到最大光感受器死亡率，GSH - GSSG和GFAP增加；（iv）在出生后第21天，小胶质细胞被激活；（v）在出生后第28天，GSH合成酶减少。（4）结论：这些发现有助于理解RP的生理病理学，并帮助我们了解氧化应激和炎症是否为治疗靶点。这些发现有助于我们理解，在RP中，氧化应激和炎症的演变及其关系是时间依赖性的。从这个意义上说，重要的是要强调这两个过程都是该疾病潜在的治疗靶点。
