Artikel
Elovanoids are novel photoreceptor survival signals relevant to AMD
Suche in Medline nach
Autoren
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Nicolas Bazan
- Neuroscience Center of Excellence, New Orleans/USA; Karolinska Institutet, Stockholm/S
| Veröffentlicht: | 5. Februar 2020 |
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Gliederung
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Background: The RPE and PRC relationship restores adversities to homeostasis. DHA is a membrane component necessary for vision that is decreased in AMD. The genetic ablation of Adiponectin Receptor 1 (AdipoR1) blocks DHA uptake, reduces phosphatidylcholine (PC)-containing Very Long Chain Polyunsaturated Fatty Acids (VLC-PUFA), and leads to PRC death. Genetic ablation of the protein leads to “flecked” retinal degeneration. AdipoR1 polymorphisms are in AMD. DHA is the precursor of docosanoids (neuroprotectin D1; NPD1) and of novel mediators called elovanoids, RPE and PRC survival promoters.
Methods: AMD and control retinas were analyzed by OCT, by MALDI molecular imaging, and by LC-MS/MS precursor/mediator lipidomic analysis.
Results: Transmembrane proteins (AdipoR1 and MFRP) and cell-selective gene transcription comprise a key molecular switch in DHA retention, VLC-PUFAs formation, storage in PCs and elovanoids/NPD1 synthesis. We uncovered unique differential PC abundance in the macula and periphery, highlighting VLC-PUFA loss in AMD. MALDI imaging of early and advanced AMD retinas showed decreased PC-VLC-PUFAs in macula PRC. LC-MS/MS of peripheral and macular punches showed higher peripheral n-3 PCs (e.g., PC44:12n-3); normal periphery had more VLC-PUFAs than macula or AMD retinas. Total 54C and 56C PCs, as well as peripheral 32C and 34C PC-VLC-PUFAs, were reduced in AMD.
Conclusion: VLC-PUFAs, precursors of elovanoids, are abundant in rods (periphery); reduction in AMD may affect rod survival. Conversely, AMD-triggering events impair rod VLC-PUFA synthesis. If DHA regulation is decreased in AMD, causing VLC-PUFA reduction, peripheral rods may show early changes in retinal DHA/VLC-PUFA lipidome. VLC-PUFA reduction may reflect impaired synthesis of elovanoids, key protective mediators. Overall, we find decreased DHA retention, VLC-PUFA formation, storage in PCs and elovanoids/NPD1 synthesis in AMD. Thus, when disrupted, these uncovered mechanisms lead to onset and progression of dry-form AMD and may represent a new therapeutic target. (Supported by NIH EY005121 and by EENT Foundation)
