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Updated: May 28, 2025
A Protocol to Evaluate and Quantify Retinal Pigmented Epithelium Pathologies in Mouse Models of Age-Related Macular Degeneration
Published on: March 10, 2023
Association Between C22:5-Containing Lipids and RPE Pathologies in Mice with Tmem135 Overexpression
Michael Landowski1,2, Sakae Ikeda1,2, Akihiro Ikeda3,4
1Department of Medical Genetics, University of Wisconsin-Madison, Madison, WI, USA.
Abstract:
Dysregulation of lipid metabolism has been linked with risk for age-related retinal diseases including age-related macular degeneration (AMD). However, how dysregulated lipid metabolism contributes to AMD development is unknown. In this study, we evaluated the retinal and plasma lipidomes of a mouse model displaying retinal pigmented epithelium (RPE) pathologies that are observed in AMD including RPE dysmorphia and degeneration. We found that the RPE phenotypes in mice overexpressing transmembrane protein 135 (Tmem135 TG) are correlated with retinal and plasma lipidome changes. While distinct lipid profiles were observed in the retina and plasma of Tmem135 TG mice, a common finding in both retinal and plasma lipidomes was an increase of lipids containing C22:5. This data suggests that accumulation of C22:5-containing lipids may contribute to the development of the RPE pathologies in Tmem135 TG mice.
Insights
Altered lipid metabolism, particularly increased C22:5 lipids, is linked to retinal diseases like age-related macular degeneration (AMD). This study in mice suggests these lipid changes contribute to retinal pigment epithelium (RPE) pathologies seen in AMD.
Area of Science:
- Ophthalmology
- Lipidomics
- Molecular Biology
Background:
- Dysregulation of lipid metabolism is associated with age-related retinal diseases, including age-related macular degeneration (AMD).
- The precise mechanisms by which altered lipid metabolism contributes to AMD pathogenesis remain unclear.
Purpose of the Study:
- To investigate the relationship between lipid metabolism and retinal pigment epithelium (RPE) pathologies characteristic of AMD.
- To analyze the retinal and plasma lipidomes in a mouse model overexpressing transmembrane protein 135 (Tmem135 TG), which exhibits RPE abnormalities.
Main Methods:
- Comparative analysis of retinal and plasma lipid profiles in Tmem135 TG mice and control littermates.
- Assessment of RPE morphology and function in the Tmem135 TG mouse model.
Main Results:
- Tmem135 TG mice displayed distinct retinal and plasma lipidome alterations.
- A significant increase in lipids containing the C22:5 fatty acid was observed in both the retina and plasma of Tmem135 TG mice.
- These lipid changes correlated with observed RPE dysmorphia and degeneration.
Conclusions:
- Overexpression of Tmem135 leads to significant changes in lipid metabolism within the retina and plasma.
- Accumulation of C22:5-containing lipids may play a critical role in the development of RPE pathologies associated with AMD.
- This study provides insights into the role of lipid dysregulation in AMD pathogenesis.
