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. 2020 Nov 9;10:391. doi: 10.1038/s41398-020-01080-1

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — Dysregulation in the uptake and metabolism of omega-3 fatty acid docosahexaenoic acid (DHA) and its derivatives in the retina and the brain are associated with retinal abnormalities and early events in the pathogenesis of schizophrenia. Adiponectin receptor 1 (AdipoR1), primarily found in the eye and brain with little expression in other tissues, captures DHA in both the retina and brain. DHA is an important precursor of VLC-PUFAs (32:6n-3 and 34:6n-3), which subsequently turn into elovanoids (ELVs, ELV-N32, and ELV-N34) catalyzed by the elongase enzyme, specifically through the elongation of very-long-chain fatty acids-4 (ELOVL4). In addition, DHA is the precursor of neuroprotectin D1 (NPD1). Both ELVs and NPD1 sustain the integrity of the pigment epithelial cells (PECs) as well as photoreceptor cells (PRCs) in the retina. Dysregulation of DHA uptake and conversion into ELVs and NPD1 can disrupt the structural and functional integrity of the retina, leading to retinal abnormalities. In the brain, NPD1, converted from its precursor DHA, is involved in the protection of dopaminergic circuits. Dysregulation of DHA uptake and its conversion into NPD1 is associated with the loss of dopamine neurons, which is proposed to contribute to the pathogenesis of schizophrenia.