Department of Biomedical Sciences, Faculty of Health Sciences, Institute of Biomedical Sciences, Cardenal Herrera-CEU University, CEU Universities, 46115 Valencia, Spain.
Biomolecules. 2023 Aug 22;13(9):1277. doi: 10.3390/biom13091277.
(1) Background: the aim of this work was to study microglia and autophagy alterations in a one retinitis pigmentosa (RP) model at different stages of the disease (when rods are dying and later, when there are almost no rods, and cones are the cells that die. (2) Methods: rd1 mice were used and retinas obtained at postnatal days (PN) 11, 17, 28, 35, and 42. Iba1 (ionized calcium-binding adapter molecule 1) was the protein selected to study microglial changes. The macroautophagy markers Beclin-1, Atg5, Atg7, microtubule-associated protein light chain 3 (LC3), and lysosomal-associated membrane protein 2 (LAMP2) (involved in chaperone-mediated autophagy (CMA)) were determined. (3) Results: the expression of Iba1 was increased in rd1 retinas compared to the control group at PN17 (after the period of maximum rod death), PN28 (at the beginning of the period of cone death), and PN42. The number of activated (ameboid) microglial cells increased in the early ages of the retinal degeneration and the deactivated forms (branched cells) in more advanced ages. The macroautophagy markers Atg5 at PN11, Atg7 and LC3II at PN17, and Atg7 again at PN28 were decreased in rd1 retinas. At PN35 and PN42, the results reveal alterations in LAMP2A, a marker of CMA in the retina of rd1 mice. (4) Conclusions: we can conclude that during the early phases of retinal degeneration in the rd1 mouse, there is an alteration in microglia and a decrease in the macroautophagy cycle. Subsequently, the CMA is decreased and later on appears activated as a compensatory mechanism.
(1) 背景:本研究旨在研究一种视网膜色素变性(RP)模型在疾病不同阶段(当视杆细胞死亡,随后当几乎没有视杆细胞,而视锥细胞是死亡的细胞时)中小胶质细胞和自噬的改变。(2) 方法:使用 rd1 小鼠,在出生后第 11、17、28、35 和 42 天获取视网膜。选择离子钙结合衔接分子 1(Iba1)作为研究小胶质细胞变化的蛋白。测定巨自噬标志物 Beclin-1、Atg5、Atg7、微管相关蛋白轻链 3(LC3)和溶酶体相关膜蛋白 2(LAMP2)(参与伴侣介导的自噬(CMA))。(3) 结果:与对照组相比,rd1 视网膜在 PN17(视杆细胞死亡高峰期后)、PN28(视锥细胞死亡初期)和 PN42(视网膜变性早期)时 Iba1 的表达增加。在视网膜变性的早期,激活(阿米巴样)小胶质细胞的数量增加,而在较晚期则为去激活(分支状细胞)形式。rd1 视网膜中的巨自噬标志物 Atg5 在 PN11、Atg7 和 LC3II 在 PN17 以及 Atg7 再次在 PN28 时减少。在 PN35 和 PN42,结果表明 rd1 小鼠视网膜中的 CMA 标志物 LAMP2A 发生改变。(4) 结论:我们可以得出结论,在 rd1 小鼠视网膜变性的早期阶段,小胶质细胞发生改变,巨自噬循环减少。随后,CMA 减少,随后作为一种代偿机制而被激活。