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Vps35-deficiency impairs SLC4A11 trafficking and promotes corneal dystrophy

Wei Liu1,2,3, Fu-Lei Tang1,2,4, Sen Lin1,2,3

  • 1Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia, United States of America.

Plos One
|September 22, 2017
PubMed

Insights

Vacuolar protein sorting 35 (Vps35) plays a key role in preventing corneal dystrophy. Vps35 deficiency impairs SLC4A11 transport, leading to corneal degeneration and potential therapeutic targets.

Area of Science:

  • Cell Biology
  • Ophthalmology
  • Neuroscience

Background:

  • Vps35 (vacuolar protein sorting 35) is a core retromer component essential for endosome-to-Golgi retrieval of transmembrane proteins.
  • Retromer dysfunction is linked to neurodegenerative diseases like Parkinson's and Alzheimer's.
  • The role of Vps35 in ocular health and corneal degenerative disorders is largely unexplored.

Purpose of the Study:

  • To investigate the function of Vps35 in the cornea.
  • To determine if Vps35 deficiency contributes to corneal dystrophy.
  • To identify Vps35/retromer cargo proteins involved in corneal health.

Main Methods:

  • Expression analysis of Vps35 in mouse and human cornea.
  • Phenotypic characterization of Vps35+/- mouse corneas.
  • Assessment of corneal cell densities, organization, and epithelial cell proliferation in Vps35-deficient mice.
  • Analysis of SLC4A11 cell surface targeting in Vps35-deficient cells and corneas.

Main Results:

  • Vps35 is expressed in both mouse and human corneas.
  • Vps35+/- mice exhibit corneal dystrophy features, including reduced cell densities, disorganization, Descemet membrane abnormalities, and edema.
  • Corneal epithelial cell proliferation is diminished in Vps35-deficient mice.
  • Cell surface targeting of the corneal endothelium transporter SLC4A11 is impaired in Vps35-deficient contexts.

Conclusions:

  • Vps35 plays a critical role in maintaining corneal integrity.
  • Vps35 deficiency leads to corneal dystrophy phenotypes in mice.
  • SLC4A11 is identified as a Vps35/retromer cargo, and its impaired trafficking contributes to Vps35-related corneal dystrophy.

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