Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
Int J Mol Sci. 2021 Oct 26;22(21):11557. doi: 10.3390/ijms222111557.
Progranulin (PGRN) is a secreted glycoprotein that regulates numerous cellular processes. The role of PGRN as a regulator of lysosomes has recently received attention. The purpose of this study was to characterize the retinal phenotype in mature PGRN knockout () mice. The a-wave amplitude of scotopic electroretinogram and outer nuclear thickness were significantly reduced at 6 months of age in mice compared to wild-type () mice. In mice, retinal microglial cells accumulated on the retinal pigment epithelium (RPE) apical layer, and the number of infiltrated microglia and white fundus lesions between 2 and 6 months of age showed a close affinity. In mice, PGRN was located in the retina, while the strongest PGRN signals were detected in the RPE-choroid. The different effects of PGRN deficiency on the expression of lysosomal proteins between the retina and RPE-choroid were demonstrated. Our data suggest that the subretinal translocation of microglia is a characteristic phenotype in the retina of mature PGRN knockout mice. The different effects of PGRN deficiency on the expression of lysosomal proteins between the retina and RPE-choroid might modulate microglial dynamics in PGRN knockout mice.
颗粒体蛋白聚糖 (PGRN) 是一种分泌性糖蛋白，可调节多种细胞过程。PGRN 作为溶酶体调节剂的作用最近受到了关注。本研究旨在描述成熟 PGRN 敲除（）小鼠的视网膜表型。与野生型（）小鼠相比，6 月龄时，暗适应视网膜电图的 a 波振幅和外核层厚度在（）小鼠中明显降低。在（）小鼠中，视网膜小胶质细胞在视网膜色素上皮（RPE）顶层层积，并且在 2 至 6 月龄之间浸润小胶质细胞的数量和白色眼底病变显示出密切的亲和力。在（）小鼠中，PGRN 位于视网膜中，而在 RPE-脉络膜中检测到最强的 PGRN 信号。研究表明，PGRN 缺乏对视网膜和 RPE-脉络膜之间溶酶体蛋白表达的不同影响。我们的数据表明，成熟 PGRN 敲除小鼠视网膜中小胶质细胞的视网膜下易位是其特征性表型。PGRN 缺乏对视网膜和 RPE-脉络膜之间溶酶体蛋白表达的不同影响可能调节 PGRN 敲除小鼠中小胶质细胞的动力学。
