Sfrp1 deficiency makes retinal photoreceptors prone to degeneration

Sci Rep. 2020 Mar 20;10(1):5115. doi: 10.1038/s41598-020-61970-8.


Millions of individuals worldwide suffer from impaired vision, a condition with multiple origins that often impinge upon the light sensing cells of the retina, the photoreceptors, affecting their integrity. The molecular components contributing to this integrity are however not yet fully understood. Here we have asked whether Secreted Frizzled Related Protein 1 (SFRP1) may be one of such factors. SFRP1 has a context-dependent function as modulator of Wnt signalling or of the proteolytic activity of A Disintegrin And Metalloproteases (ADAM) 10, a main regulator of neural cell-cell communication. We report that in Sfrp1-/- mice, the outer limiting membrane (OLM) is discontinuous and the photoreceptors disorganized and more prone to light-induced damage. Sfrp1 loss significantly enhances the effect of the Rpe65Leu450Leu genetic variant -present in the mouse genetic background- which confers sensitivity to light-induced stress. These alterations worsen with age, affect visual function and are associated to an increased proteolysis of Protocadherin 21 (PCDH21), localized at the photoreceptor outer segment, and N-cadherin, an OLM component. We thus propose that SFRP1 contributes to photoreceptor fitness with a mechanism that involves the maintenance of OLM integrity. These conclusions are discussed in view of the broader implication of SFRP1 in neurodegeneration and aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM10 Protein / metabolism
  • Amyloid Precursor Protein Secretases / metabolism
  • Animals
  • Cadherins / metabolism
  • Cell Communication / genetics
  • Cell Membrane / pathology*
  • Light / adverse effects
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Photoreceptor Cells, Vertebrate / pathology*
  • Retinal Degeneration / pathology*
  • Vision Disorders / genetics
  • Vision Disorders / pathology*
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway / genetics
  • cis-trans-Isomerases / genetics


  • Cadherins
  • Cdh2 protein, mouse
  • Membrane Proteins
  • Pcdh21 protein, mouse
  • Sfrp1 protein, mouse
  • Wnt Proteins
  • retinoid isomerohydrolase
  • Amyloid Precursor Protein Secretases
  • ADAM10 Protein
  • Adam10 protein, mouse
  • cis-trans-Isomerases