Photoreceptor preservation induced by intravitreal controlled delivery of GDNF and GDNF/melatonin in rhodopsin knockout mice.

Abstract

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: (-/-); 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: (-/-) mice. These intraocular drug delivery systems enable the efficient codelivery of therapeutically active substances for the treatment of retinal diseases.