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Updated: Jan 31, 2026

Author Spotlight: Advancing Vision Restoration - Stem Cell-Based Therapy for Retinal Diseases
Published on: October 6, 2023
Photoreceptor preservation induced by intravitreal controlled delivery of GDNF and GDNF/melatonin in rhodopsin
Cristina García-Caballero1, Burke Lieppman2, Alicia Arranz-Romera1
1Pharmaceutical Innovation in Ophthalmology Research Group, UCM 920415, Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University, Madrid, Spain.
Purpose:
To evaluate the potential of a poly(lactic-co-glycolic acid) (PLGA)-based slow release formulation of glial cell line-derived neurotrophic factor (GDNF) alone or in combination with melatonin to rescue photoreceptors in a mouse model of retinal degeneration.
Methods:
GDNF and GDNF/melatonin-loaded PLGA microspheres (MSs) were prepared using a solid-in-oil-in-water emulsion solvent extraction-evaporation technique. A combination of PLGA and vitamin E (VitE) was used to create the microcarriers. The structure, particle size, encapsulation efficiency, and in vitro release profile of the microparticulate formulations were characterized. Microparticulate systems (non-loaded, GDNF, and GDNF/melatonin-loaded MSs) were administered intravitreally to 3-week-old rhodopsin knockout mice (rho (-/-); n=7). The functional neuroprotective effect was assessed with electroretinography at 6, 9, and 12 weeks old. The rescue of the structure was determined with photoreceptor quantification at 12 weeks (9 weeks after administration of MSs). Immunohistochemistry for photoreceptor, glial, and proliferative markers was also performed.
Results:
The microspheres were able to deliver GDNF or to codeliver GDNF and melatonin in a sustained manner. Intravitreal injection of GDNF or GDNF/melatonin-loaded MSs led to partial functional and structural rescue of photoreceptors compared to blank microspheres or vehicle. No significant intraocular inflammatory reaction was observed after intravitreal injection of the microspheres.
Conclusions:
A single intravitreal injection of GDNF or GDNF/melatonin-loaded microspheres in the PLGA/VitE combination promoted the rescue of the photoreceptors in rho (-/-) mice. These intraocular drug delivery systems enable the efficient codelivery of therapeutically active substances for the treatment of retinal diseases.
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