PreprintArticleVersion 1This version is not peer-reviewed
Bioactive Glial-Derived Neurotrophic Factor From a Safe Injectable Collagen-Alginate Composite Gel Rescues Retinal Photoreceptors From Retinal Degeneration in Rabbits
Version 1
: Received: 5 August 2024 / Approved: 5 August 2024 / Online: 6 August 2024 (12:41:08 CEST)
How to cite:
Hu, T.; Zhou, T.; Goit, R. K.; Tam, K. C.; Chan, Y. K.; Lam, W.-C.; Lo, A. C. Y. Bioactive Glial-Derived Neurotrophic Factor From a Safe Injectable Collagen-Alginate Composite Gel Rescues Retinal Photoreceptors From Retinal Degeneration in Rabbits. Preprints2024, 2024080351. https://doi.org/10.20944/preprints202408.0351.v1
Hu, T.; Zhou, T.; Goit, R. K.; Tam, K. C.; Chan, Y. K.; Lam, W.-C.; Lo, A. C. Y. Bioactive Glial-Derived Neurotrophic Factor From a Safe Injectable Collagen-Alginate Composite Gel Rescues Retinal Photoreceptors From Retinal Degeneration in Rabbits. Preprints 2024, 2024080351. https://doi.org/10.20944/preprints202408.0351.v1
Hu, T.; Zhou, T.; Goit, R. K.; Tam, K. C.; Chan, Y. K.; Lam, W.-C.; Lo, A. C. Y. Bioactive Glial-Derived Neurotrophic Factor From a Safe Injectable Collagen-Alginate Composite Gel Rescues Retinal Photoreceptors From Retinal Degeneration in Rabbits. Preprints2024, 2024080351. https://doi.org/10.20944/preprints202408.0351.v1
APA Style
Hu, T., Zhou, T., Goit, R. K., Tam, K. C., Chan, Y. K., Lam, W. C., & Lo, A. C. Y. (2024). Bioactive Glial-Derived Neurotrophic Factor From a Safe Injectable Collagen-Alginate Composite Gel Rescues Retinal Photoreceptors From Retinal Degeneration in Rabbits. Preprints. https://doi.org/10.20944/preprints202408.0351.v1
Chicago/Turabian Style
Hu, T., Wai-Ching Lam and Amy Cheuk Yin Lo. 2024 "Bioactive Glial-Derived Neurotrophic Factor From a Safe Injectable Collagen-Alginate Composite Gel Rescues Retinal Photoreceptors From Retinal Degeneration in Rabbits" Preprints. https://doi.org/10.20944/preprints202408.0351.v1
Abstract
The management of vision-threatening retinal diseases remains challenging due to the lack of an effective drug delivery system. Encapsulated cell therapy (ECT) offers a promising approach for the continuous delivery of therapeutic agents without the need for immunosuppressants. In this context, an injectable and terminable collagen-alginate composite (CAC) ECT gel, designed with a Tet-on pro-caspase-8 system, was developed as a safe intraocular drug delivery platform for the sustained release of glial cell line-derived neurotrophic factor (GDNF) to treat retinal degenerative diseases (RDDs). This study examined the potential clinical application of the CAC ECT gel, focusing on its safety, performance, and termination through doxycycline (Dox) administration in the eyes of healthy New Zealand White rabbits, as well as its therapeutic efficacy in rabbits with sodium iodate (SI)-induced retinal degeneration. The findings indicated that CAC ECT gel can be safely implanted without harming the retina or lens, displaying resistance to degradation, facilitating cell attachment, and secreting bioactive GDNF. Furthermore, the GDNF levels could be modulated by the number of implants. Moreover, Dox administration was effective in terminating gel function without causing retinal damage. Notably, rabbits with retinal degeneration treated with the gels exhibited significant functional recovery in both a-wave and b-wave amplitudes and showed remarkable efficacy in reducing photoreceptor apoptosis. Given its biocompatibility, mechanical stability, controlled drug release, terminability, and therapeutic effectiveness, our CAC ECT gel presents a promising therapeutic strategy for various retinal diseases in a clinical setting, eliminating the need for immunosuppressants.
Keywords
Composite hydrogel; encapsulated cell therapy; neuroprotection; sustained drug delivery; retina
Subject
Medicine and Pharmacology, Ophthalmology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
