Presentation Date
19-10-2021 12:00 AM
Description
Abnormal lipid metabolism is the derivation of multiple retinal degenerative and blinding diseases. In the LSU Neuroscience Center, the membrane-type frizzled-related protein (MFRP), and adiponectin receptor 1 (AdipoR1) were shown to be vital to the maintenance of a healthy retinal lipidome. The two mice models of retinal degenerations Mfrprd6 and Adipor1 -/- resulted in a reduction of phospholipids containing docosahexaenoic acid (DHA; 22:6) and very long-chain polyunsaturated fatty acids (VLC-PUFAs). In a pathway involving the omega 3 fatty acids eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6), the fatty acid elongase-4 (ELOVL4) elongates the fatty acid 28:6 into VLC-PUFAs, which are precursors to potent neuroprotective molecules known as Elovanoids. Furthermore, VLC-PUFAs are important in retaining cell structure and modulating cell signaling in the visual cycle. Thus, progressive photoreceptor cell death and the subsequent onset of retinal degeneration ensues in these Mfrprd6 and Adipor1 -/- animals. Given that these lipids are essential for proper vision, it is important to decipher the specific lipid precursors and enzymes altered by the presence of a dysfunctional MFRP or the absence of Adipor1. Using organotypic culture of retina and RPE-eyecups from Mfrprd6, Adipor1 -/-, and control animals, I am employing molecular biology approaches such as western blotting and LC- MS/MS to evaluate protein expression and lipid concentrations, respectively. Lipid levels of various fatty acid intermediates within the biochemical pathways involved in synthesizing VLC- PUFAs will be analyzed. MALDI IMS imaging of retinal sections from WT, Mfrprd6, and Adipor1 - /- will be obtained to further define differences in the retinal lipidome. These findings will help us understand the role of these proteins in maintaining retinal homeostasis. Preliminary data showed a significant decrease in the concentration of EPA in Adipor1 -/- models compared to the wildtype. Conversely, there was no significant difference between DHA levels between Adipor1 -/- and the wildtype models. These results suggest that EPA has a prominent role in the VLC-PUFA synthesis pathway rather than DHA as previously believed. Additionally, the concentration of arachidonic acid (AA; 20:4) in the retinal membrane is significantly increased in the Adipor1 -/- model compared to the wildtype. This insinuates a compensatory mechanism for the decreased EPA concentration. Further experimentation with additional replicates is necessary to unveil the accurate mechanisms and pathway.
Recommended Citation
Aucoin, Alise J.; Kautzmann Guerin, Marie Audrey; Gordon, William; Prestenburg, Eric; Ji, Jeff; Perera, Rasangi; and Bazan, Nicolas, "The onset of retinal degeneration in a mutation of membrane-type frizzled-relatedprotein oradiponectin receptor 1 engages essential fatty acid impairments" (2021). Medical Student Research Poster Symposium. 6.
https://digitalscholar.lsuhsc.edu/sommrd/2021MRD/Posters/6
Included in
The onset of retinal degeneration in a mutation of membrane-type frizzled-relatedprotein oradiponectin receptor 1 engages essential fatty acid impairments
Abnormal lipid metabolism is the derivation of multiple retinal degenerative and blinding diseases. In the LSU Neuroscience Center, the membrane-type frizzled-related protein (MFRP), and adiponectin receptor 1 (AdipoR1) were shown to be vital to the maintenance of a healthy retinal lipidome. The two mice models of retinal degenerations Mfrprd6 and Adipor1 -/- resulted in a reduction of phospholipids containing docosahexaenoic acid (DHA; 22:6) and very long-chain polyunsaturated fatty acids (VLC-PUFAs). In a pathway involving the omega 3 fatty acids eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6), the fatty acid elongase-4 (ELOVL4) elongates the fatty acid 28:6 into VLC-PUFAs, which are precursors to potent neuroprotective molecules known as Elovanoids. Furthermore, VLC-PUFAs are important in retaining cell structure and modulating cell signaling in the visual cycle. Thus, progressive photoreceptor cell death and the subsequent onset of retinal degeneration ensues in these Mfrprd6 and Adipor1 -/- animals. Given that these lipids are essential for proper vision, it is important to decipher the specific lipid precursors and enzymes altered by the presence of a dysfunctional MFRP or the absence of Adipor1. Using organotypic culture of retina and RPE-eyecups from Mfrprd6, Adipor1 -/-, and control animals, I am employing molecular biology approaches such as western blotting and LC- MS/MS to evaluate protein expression and lipid concentrations, respectively. Lipid levels of various fatty acid intermediates within the biochemical pathways involved in synthesizing VLC- PUFAs will be analyzed. MALDI IMS imaging of retinal sections from WT, Mfrprd6, and Adipor1 - /- will be obtained to further define differences in the retinal lipidome. These findings will help us understand the role of these proteins in maintaining retinal homeostasis. Preliminary data showed a significant decrease in the concentration of EPA in Adipor1 -/- models compared to the wildtype. Conversely, there was no significant difference between DHA levels between Adipor1 -/- and the wildtype models. These results suggest that EPA has a prominent role in the VLC-PUFA synthesis pathway rather than DHA as previously believed. Additionally, the concentration of arachidonic acid (AA; 20:4) in the retinal membrane is significantly increased in the Adipor1 -/- model compared to the wildtype. This insinuates a compensatory mechanism for the decreased EPA concentration. Further experimentation with additional replicates is necessary to unveil the accurate mechanisms and pathway.