Disrupted Blood-Retina Lysophosphatidylcholine Transport Impairs Photoreceptor Health But Not Visual Signal Transduction

• DOI: 10.1523/jneurosci.1142-19.2019
• Publication Date: 2019-11-01T21:45:54Z
• Authors: Ekaterina S. Loba...; Kai Schuhmann; Stella Finkelstein; Tylor R. Lewis; Martha A. Cady; Ying Hao; Casey Keuthan; John D. Ash; Marie E. Burns; Andrej Shevchenko; Vadim Y. Arshavsky
• Keywords: Lysophosphatidylcholine; Visual phototransduction; Lipidome; Photoreceptor cell

Retinal photoreceptor cells contain the highest concentration of docosahexaenoic acid (DHA) in our bodies, and it has been long assumed that this is critical for supporting normal vision. Indeed, early studies using DHA dietary restriction documented reduced light sensitivity by DHA-deprived retinas. Recently, demonstrated a major route entry retina delivery across blood–retina barrier sodium-dependent lipid transporter, Mfsd2a. This discovery opened unique opportunity to analyze health function retinas Mfsd2a knock-out mouse as animal model. Our lipidome analyses −/− outer segment membranes corroborated previously reported decrease fraction DHA-containing phospholipids compensatory increase containing arachidonic acid. We also revealed an retinal content monounsaturated fatty acids reduction very chain acids. These changes could be explained combination supply concomitant upregulation several desaturases controlled sterol regulatory element-binding transcription factors, which are upregulated undergo slow progressive degeneration, with ∼30% lost age 6 months. Despite pathology, ultrastructure photoreceptors their ability produce responses were essentially normal. data demonstrate that, whereas maintaining lysophosphatidylcholine essential long-term survival, not important phototransduction. SIGNIFICANCE STATEMENT Phospholipids greatly enriched nervous system, found light-sensitive cells. In study, we analyzed consequences impaired transport barrier. have addition predictable level, affected complex, transcriptionally-driven rebuilding membrane pattern preserving overall saturation/desaturation balance phospholipids. Remarkably, these do affect but detrimental survival