Retinal Degeneration and Microglial Dynamics in Mature Progranulin-Deficient Mice
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 (<i>Grn</i><sup>−/−<...
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MDPI AG
2021
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oai:doaj.org-article:3283d62f840a41fa85d9472b6f592bc02021-11-11T17:02:21ZRetinal Degeneration and Microglial Dynamics in Mature Progranulin-Deficient Mice10.3390/ijms2221115571422-00671661-6596https://doaj.org/article/3283d62f840a41fa85d9472b6f592bc02021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11557https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Progranulin (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 (<i>Grn</i><sup>−/−</sup>) mice. The a-wave amplitude of scotopic electroretinogram and outer nuclear thickness were significantly reduced at 6 months of age in <i>Grn<sup>−/−</sup></i> mice compared to wild-type (<i>Grn<sup>+/+</sup></i>) mice. In <i>Grn<sup>−/−</sup></i> 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 <i>Grn<sup>+/+</sup></i> 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.Kei TakahashiShinsuke NakamuraMasamitsu ShimazawaHideaki HaraMDPI AGarticleprogranulinretinaretinal pigment epitheliummicroglialysosomeneuronal ceroid lipofuscinosisBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11557, p 11557 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
progranulin retina retinal pigment epithelium microglia lysosome neuronal ceroid lipofuscinosis Biology (General) QH301-705.5 Chemistry QD1-999 |
| spellingShingle |
progranulin retina retinal pigment epithelium microglia lysosome neuronal ceroid lipofuscinosis Biology (General) QH301-705.5 Chemistry QD1-999 Kei Takahashi Shinsuke Nakamura Masamitsu Shimazawa Hideaki Hara Retinal Degeneration and Microglial Dynamics in Mature Progranulin-Deficient Mice |
| description |
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 (<i>Grn</i><sup>−/−</sup>) mice. The a-wave amplitude of scotopic electroretinogram and outer nuclear thickness were significantly reduced at 6 months of age in <i>Grn<sup>−/−</sup></i> mice compared to wild-type (<i>Grn<sup>+/+</sup></i>) mice. In <i>Grn<sup>−/−</sup></i> 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 <i>Grn<sup>+/+</sup></i> 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. |
| format |
article |
| author |
Kei Takahashi Shinsuke Nakamura Masamitsu Shimazawa Hideaki Hara |
| author_facet |
Kei Takahashi Shinsuke Nakamura Masamitsu Shimazawa Hideaki Hara |
| author_sort |
Kei Takahashi |
| title |
Retinal Degeneration and Microglial Dynamics in Mature Progranulin-Deficient Mice |
| title_short |
Retinal Degeneration and Microglial Dynamics in Mature Progranulin-Deficient Mice |
| title_full |
Retinal Degeneration and Microglial Dynamics in Mature Progranulin-Deficient Mice |
| title_fullStr |
Retinal Degeneration and Microglial Dynamics in Mature Progranulin-Deficient Mice |
| title_full_unstemmed |
Retinal Degeneration and Microglial Dynamics in Mature Progranulin-Deficient Mice |
| title_sort |
retinal degeneration and microglial dynamics in mature progranulin-deficient mice |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/3283d62f840a41fa85d9472b6f592bc0 |
| work_keys_str_mv |
AT keitakahashi retinaldegenerationandmicroglialdynamicsinmatureprogranulindeficientmice AT shinsukenakamura retinaldegenerationandmicroglialdynamicsinmatureprogranulindeficientmice AT masamitsushimazawa retinaldegenerationandmicroglialdynamicsinmatureprogranulindeficientmice AT hideakihara retinaldegenerationandmicroglialdynamicsinmatureprogranulindeficientmice |
| _version_ |
1718432169170305024 |