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Membrane-type frizzled-related protein regulates lipidome and transcription for photoreceptor function

Marie-Audrey I Kautzmann1, William C Gordon1, Bokkyoo Jun1

  • 1Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|January 10, 2020
PubMed

Insights

Membrane-type frizzled-related protein (MFRP) and adiponectin receptor 1 (AdipoR1) are crucial for photoreceptor membrane organization and visual function. Loss of these proteins leads to retinal degeneration and impaired fatty acid enrichment.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Neuroscience

Background:

  • Photoreceptor (PRC) membrane organization and gene regulation are key to vision and retinal degenerations.
  • Understanding the molecular mechanisms behind these processes is critical for treating blindness.

Purpose of the Study:

  • To investigate the role of membrane-type frizzled-related protein (MFRP) in photoreceptor membrane organization and docosahexaenoic acid (DHA) enrichment.
  • To compare the function of MFRP with adiponectin receptor 1 (AdipoR1) in retinal lipid metabolism.

Main Methods:

  • Utilized Mfrprd6 mice models exhibiting PRC degeneration.
  • Employed untargeted imaging mass spectrometry to analyze retinal lipid composition.
  • Assessed gene expression changes in pro-inflammatory and PRC function-related pathways.

Main Results:

  • MFRP and AdipoR1 are involved in DHA enrichment in photoreceptors.
  • Reduced phospholipids containing DHA and very long-chain polyunsaturated fatty acids (VLC-PUFAs) were observed in Adipor1-/- and Mfrprd6 retinas.
  • Increased pro-inflammatory signaling and decreased PRC function gene expression were found in both mutant models.

Conclusions:

  • MFRP and AdipoR1 are essential for maintaining retinal lipidome membrane organization and visual function.
  • Dysfunction of these proteins contributes to the early pathology of retinal degenerative diseases.
  • These findings offer insights into the molecular basis of inherited retinal diseases and potential therapeutic targets.
Keywords:
Adipor1RPE cellVLC‐PUFAsinflammatory signalingmatrix‐assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS)retinal degenerations

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