RPE Cells Engulf Microvesicles Secreted by Degenerating Rod Photoreceptors

Philip Ropelewski1, Yoshikazu Imanishi2

  • 1Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.

Eneuro
|May 8, 2020
PubMed

Insights

Photoreceptor cells in blinding disorders secrete microvesicles containing mislocalized rhodopsin. Retinal pigment epithelial cells engulf these rhodopsin-laden microvesicles, offering insights into protein sorting and photoreceptor health.

Area of Science:

  • Cell Biology
  • Ophthalmology
  • Genetics

Background:

  • Rhodopsin mislocalization to the inner segment plasma membrane (IS PM) occurs in blinding disorders like autosomal-dominant retinitis pigmentosa.
  • Photoreceptor cells release rhodopsin-containing microvesicles into the extracellular space in these conditions.

Purpose of the Study:

  • To investigate the engulfment of rhodopsin-laden microvesicles by retinal pigment epithelial (RPE) cells.
  • To elucidate the sorting mechanism for packaging mutant rhodopsin into microvesicles.

Main Methods:

  • Utilized a *Xenopus laevis* model expressing class I mutant rhodopsin or Na+/K+-ATPase (NKA) fused to Dendra2.
  • Fluorescently labeled microvesicles to track their uptake by RPE cells.

Main Results:

  • Demonstrated that RPE cells can engulf microvesicles containing rhodopsin.
  • Identified a unique sorting mechanism that specifically packages class I mutant rhodopsin, but not NKA, into microvesicles.
  • Showed that NKA is normally degraded intracellularly and not shed in microvesicles.

Conclusions:

  • RPE cells actively clear rhodopsin-laden microvesicles secreted by photoreceptors.
  • A specific protein sorting pathway exists for mutant rhodopsin in photoreceptor IS PM.
  • These findings provide new understanding of protein homeostasis and cellular waste management in photoreceptors.

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