{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T01:32:51Z","timestamp":1780709571498,"version":"3.54.1"},"reference-count":39,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2212\/\u2212) mice. The a-wave amplitude of scotopic electroretinogram and outer nuclear thickness were significantly reduced at 6 months of age in Grn\u2212\/\u2212 mice compared to wild-type (Grn+\/+) mice. In Grn\u2212\/\u2212 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.<\/jats:p>","DOI":"10.3390\/ijms222111557","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T23:54:33Z","timestamp":1635292473000},"page":"11557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Retinal Degeneration and Microglial Dynamics in Mature Progranulin-Deficient Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Kei","family":"Takahashi","sequence":"first","affiliation":[{"name":"Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masamitsu","family":"Shimazawa","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Hara","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrn.2017.36","article-title":"Progranulin, lysosomal regulation and neurodegenerative disease","volume":"18","author":"Kao","year":"2017","journal-title":"Nat. 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