Modulation of Tmem135 Leads to Retinal Pigmented Epithelium Pathologies in Mice
| Autor: | Franky Shi, Daniel Western, Abigail Johnson, Wei-Hua Lee, Adrienne Race, Bikash R. Pattnaik, Evelyn Santoirre, Pawan K Shahi, Jonathan Benson, Akihiro Ikeda, Michael Landowski, Sakae Ikeda, Samuel Grindel, Marvin Gao |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Mitochondrial Diseases Blotting Western Cell Count Retinal Pigment Epithelium Mitochondrion Biology Real-Time Polymerase Chain Reaction Mitochondrial Proteins 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Western blot medicine Electroretinography Animals Cells Cultured Retina medicine.diagnostic_test aging Retinal Degeneration Membrane Proteins Retinal Immunohistochemistry eye diseases Cell biology mitochondria Mice Inbred C57BL Disease Models Animal Microscopy Electron 030104 developmental biology medicine.anatomical_structure Phenotype Vacuolization chemistry Retinal Cell Biology Gene Expression Regulation Mutation 030221 ophthalmology & optometry sense organs RPE Erg |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 0146-0404 |
| Popis: | Purpose Aging is a critical risk factor for the development of retinal diseases, but how aging perturbs ocular homeostasis and contributes to disease is unknown. We identified transmembrane protein 135 (Tmem135) as a gene important for regulating retinal aging and mitochondrial dynamics in mice. Overexpression of Tmem135 causes mitochondrial fragmentation and pathologies in the hearts of mice. In this study, we examine the eyes of mice overexpressing wild-type Tmem135 (Tmem135 TG) and compare their phenotype to Tmem135 mutant mice. Methods Eyes were collected for histology, immunohistochemistry, electron microscopy, quantitative PCR, and Western blot analysis. Before tissue collection, electroretinography (ERG) was performed to assess visual function. Mouse retinal pigmented epithelium (RPE) cultures were established to visualize mitochondria. Results Pathologies were observed only in the RPE of Tmem135 TG mice, including degeneration, migratory cells, vacuolization, dysmorphogenesis, cell enlargement, and basal laminar deposit formation despite similar augmented levels of Tmem135 in the eyecup (RPE/choroid/sclera) and neural retina. We observed reduced mitochondria number and size in the Tmem135 TG RPE. ERG amplitudes were decreased in 365-day-old mice overexpressing Tmem135 that correlated with reduced expression of RPE cell markers. In Tmem135 mutant mice, RPE cells are thicker, smaller, and denser than their littermate controls without any signs of degeneration. Conclusions Overexpression and mutation of Tmem135 cause contrasting RPE abnormalities in mice that correlate with changes in mitochondrial shape and size (overfragmented in TG vs. overfused in mutant). We conclude proper regulation of mitochondrial homeostasis by TMEM135 is critical for RPE health. |
| Databáze: | OpenAIRE |
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