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Related Experiment Video

Updated: Jun 12, 2025

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Bioactive Glial-Derived Neurotrophic Factor from a Safe Injectable Collagen-Alginate Composite Gel Rescues Retinal

Tingyu Hu1, Ting Zhou1, Rajesh Kumar Goit1,2

  • 1Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Marine Drugs
|September 27, 2024
PubMed
Summary

A novel injectable gel for encapsulated cell therapy (ECT) safely delivers glial-cell-line-derived neurotrophic factor (GDNF) to treat retinal diseases. This therapy is controllable and can be terminated, showing significant functional recovery in animal models.

Keywords:
HEK cellscollagen–alginate composite hydrogeldoxycyclineelectroretinographyencapsulated cell therapyintravitrealneuroprotectionretinasustained drug delivery

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Area of Science:

  • Ophthalmology
  • Biomaterials Science
  • Regenerative Medicine

Background:

  • Effective drug delivery for vision-threatening retinal diseases is limited.
  • Encapsulated cell therapy (ECT) offers sustained therapeutic agent delivery without immunosuppression.

Purpose of the Study:

  • To evaluate a novel injectable collagen-alginate composite (CAC) ECT gel for sustained glial-cell-line-derived neurotrophic factor (GDNF) delivery.
  • To assess the safety, performance, and terminability of the CAC ECT gel in rabbit models for treating retinal degenerative diseases.

Main Methods:

  • Development of an injectable and terminable CAC ECT gel with a Tet-on pro-caspase-8 system.
  • In vivo studies in New Zealand White rabbits (healthy and sodium-iodate induced retinal degeneration) to assess safety, GDNF release, and therapeutic efficacy.
  • Evaluation of gel termination using doxycycline (Dox) administration.

Main Results:

  • The CAC ECT gel demonstrated safe intraocular implantation without retinal or lens damage.
  • The gel exhibited degradation resistance, promoted cell attachment, and secreted bioactive GDNF, with controllable release levels.
  • Dox administration effectively terminated gel function without adverse effects.
  • Treated rabbits showed significant retinal function recovery (a-wave and b-wave amplitudes) and reduced photoreceptor apoptosis.

Conclusions:

  • The developed CAC ECT gel is a safe, biocompatible, and mechanically stable platform for intraocular drug delivery.
  • The gel offers controlled, terminable GDNF release, presenting a promising therapeutic strategy for retinal diseases without immunosuppressants.