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September 5, 2026Drug Delivery and Translational ResearchOpen Access

αB-crystallin elastin-like polypeptides for sustained ocular drug delivery

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Authors

SASara Aly AttiaATAmanda M. TseARAshley Ramirez

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Overview

Preclinical study demonstrates sustained intraocular retention and chaperone activity of cry-polypeptides in retinal models, highlighting a new therapeutic strategy for macular degeneration.

Key Points

  • To engineer αB-crystallin chaperone peptides linked with elastin-like polypeptides for extended intraocular retention and sustained relief from unfolded protein response stress in retinal disorders.
  • Engineered two phase-separating constructs (cry-SI and cry-V96) and evaluated their chaperone efficacy using tau protein aggregation and fibril disaggregation assays.
  • Assessed unfolded protein response attenuation in tunicamycin-stressed human retinal pigment epithelium cells, subcellular distribution via Western blotting, and proteomic profiling with LC-MS/MS.
  • Administered lead construct cry-V96 via intravitreal injection in rabbit eyes to determine depot formation, ocular retention, and safety using fluorescence imaging and optical coherence tomography.
  • Construct cry-V96 exhibited superior chaperone activity by potently inhibiting tau seeding, disaggregating fibrils, and attenuating PERK/ATF-4/CHOP endoplasmic reticulum stress signaling in retinal cells.
  • Both cry-ELP constructs displayed enhanced cellular uptake and stress-dependent nuclear localization compared to controls, with mass spectrometry identifying 59 selectively enriched proteins linked to proteostasis.
  • In rabbit eyes, cry-V96 formed a sustained intravitreal depot with extended retention and demonstrated no ocular toxicity on optical coherence tomography or fluorescence imaging.

Cite This Study

Attia et al. (2026) studied this question.

synapsesocial.com/papers/6a9bd3c76b95aff0620eaf5chttps://doi.org/10.1007/s13346-026-02210-w
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