1. Retinal Degeneration and Microglial Dynamics in Mature Progranulin-Deficient Mice.
- Author
-
Takahashi K, Nakamura S, Shimazawa M, and Hara H
- Subjects
- Animals, Brain metabolism, Brain pathology, Disease Models, Animal, Lysosomes metabolism, Lysosomes pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Retinal Pigment Epithelium metabolism, Retinal Pigment Epithelium pathology, Microglia metabolism, Microglia pathology, Progranulins metabolism, Retina metabolism, Retina pathology, Retinal Degeneration metabolism, Retinal Degeneration pathology
- Abstract
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 ( Grn
-/- ) mice. The a-wave amplitude of scotopic electroretinogram and outer nuclear thickness were significantly reduced at 6 months of age in Grn-/- mice compared to wild-type ( Grn+/+ ) mice. In Grn-/- 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 Grn+/+ 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. more...- Published
- 2021
- Full Text
- View/download PDF