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.
Highlights
Retinal degeneration leading to visual dysfunction and blindness has been reported as a typical symptom in patients with frontotemporal degeneration (FTD) and neuronal ceroid lipofuscinosis (NCL) with GRN gene mutations [7,17]
Progressive retinal degeneration and retinal deposits of autofluorescent aggregates were observed in a mouse model of CLN11 disease [6,13,14]
We analyzed the retinal phenotype of PGRN knockout mice (Grn−/− ) in detail
Summary
Progranulin (PGRN) is a secreted glycoprotein by neuron and immune cells, which has been reported to regulate numerous cellular processes, including cell survival, inflammation, and protein clearance [1]. Evidence supporting a role for PGRN in the lysosome includes its localization to these bodies, the fact that PGRN-deficient mice demonstrate increased reactivity to some lysosomal proteins, as well as its influence on the acidification of lysosomes [2,3]. These results support the role of PGRN in regulating the formation and function of lysosomes
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