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Dynamic Inner Blood Retina Barrier Disruption in Retinitis Pigmentosa.

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Inner blood-retina barrier (iBRB) disruption contributes to retinitis pigmentosa (RP) vascular changes. Stabilizing retinal vasculature may offer a gene-agnostic treatment for this inherited retinal degeneration.

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Area of Science:

  • Ophthalmology
  • Genetics
  • Vascular Biology

Background:

  • Retinitis pigmentosa (RP) is a common inherited retinal degeneration with poorly understood vascular contributions.
  • Inner blood-retina barrier (iBRB) disruption is implicated in neurological deficits but understudied in RP.

Purpose of the Study:

  • To examine retinal vascular changes in mouse models of RP.
  • To investigate the role of iBRB integrity in RP pathogenesis.
  • To assess iBRB integrity in human RP patients.

Main Methods:

  • Utilized Rho-/-, Rd10, and Rpe65D477G mouse models of RP, some on a claudin-5 heterozygous background.
  • Quantitatively assessed iBRB integrity in 14 RP patients with RHO or RPE65 variants.

Main Results:

  • RP models exhibited decreased perfusion and disrupted retinal vascular plexuses.
  • Specific loss of deeper vascular plexuses in Rho-/- and Rd10 models; global CLDN5 loss in Rpe65D477G models.
  • Human RP patients showed temporal iBRB changes mirroring preclinical models.

Conclusions:

  • This study provides the first quantitative profiling of iBRB disruption in RP.
  • Findings suggest iBRB integrity is compromised in RP.
  • Retinal vascular stabilization may be a potential gene-agnostic therapeutic strategy for RP.