Related Experiment Video
Updated: Oct 25, 2025
Slow-release Drug Delivery through Elvax 40W to the Rat Retina: Implications for the Treatment of Chronic Conditions
Published on: September 17, 2014
Retinal Protection by Sustained Nanoparticle Delivery of Oncostatin M and Ciliary Neurotrophic Factor Into Rodent
Jing-Yan Yang1,2, Bin Lu1, Qiang Feng3
1Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Purpose:
Retinitis pigmentosa (RP) is caused by mutations in more than 60 genes. Mutation-independent approaches to its treatment by exogeneous administration of neurotrophic factors that will preserve existing retinal anatomy and visual function are a rational strategy. Ciliary neurotrophic factor (CNTF) and oncostatin M (OSM) are two potent survival factors for neurons. However, growth factors degrade rapidly if administered directly. A sustained delivery of growth factors is required for translating their potential therapeutic benefit into patients.
Methods:
Stable and biocompatible nanoparticles (NP) that incorporated with CNTF and OSM (CNTF- and OSM-NP) were formulated. Both NP-trophic factors were tested in vitro using photoreceptor progenitor cells (PPC) and retinal ganglion progenitor cells (RGPC) derived from induced pluripotent stem cells and in vivo using an optic nerve crush model for glaucoma and the Royal College of Surgeons rat, model of RP (n = 8/treatment) by intravitreal delivery. Efficacy was evaluated by electroretinography and optokinetic response. Retinal histology and a whole mount analysis were performed at the end of experiments.
Results:
Significant prosurvival and pro-proliferation effects of both complexes were observed in both photoreceptor progenitor cells and RGPC in vitro. Importantly, significant RGC survival and preservation of vision and photoreceptors in both complex-treated animals were observed compared with control groups.
Conclusions:
These results demonstrate that NP-trophic factors are neuroprotective both in vitro and in vivo. A single intravitreal delivery of both NP-trophic factors offered neuroprotection in animal models of retinal degeneration.
Translational Relevance:
Sustained nanoparticle delivery of neurotrophic factors may offer beneficial effects in slowing down progressive retinal degenerative conditions, including retinitis pigmentosa, age-related macular degeneration, and glaucoma.
Insights
Nanoparticles delivering neurotrophic factors like CNTF and OSM show promise for treating retinal degeneration. A single intravitreal injection preserved vision and retinal cells in animal models of retinitis pigmentosa and glaucoma.
Area of Science:
- Ophthalmology
- Neuroscience
- Biotechnology
Background:
- Retinitis pigmentosa (RP) and other retinal degenerative diseases stem from mutations in numerous genes.
- Current treatments often focus on gene-specific mutations, highlighting the need for mutation-independent therapeutic strategies.
- Neurotrophic factors like ciliary neurotrophic factor (CNTF) and oncostatin M (OSM) show potential for neuronal survival but degrade rapidly when administered directly.
Purpose of the Study:
- To develop and evaluate sustained-release nanoparticles (NP) for delivering CNTF and OSM.
- To assess the neuroprotective efficacy of CNTF- and OSM-loaded nanoparticles in vitro and in vivo models of retinal degeneration.
Main Methods:
- Formulated stable, biocompatible nanoparticles incorporating CNTF and OSM (CNTF- and OSM-NP).
- Tested NP-trophic factors in vitro on photoreceptor progenitor cells (PPC) and retinal ganglion progenitor cells (RGPC).
- Evaluated efficacy in vivo using optic nerve crush (glaucoma model) and Royal College of Surgeons (RP model) rats via intravitreal delivery, assessing electroretinography, optokinetic response, and retinal histology.
Main Results:
- CNTF- and OSM-NP demonstrated significant prosurvival and pro-proliferation effects on PPC and RGPC in vitro.
- In vivo studies showed significant retinal ganglion cell (RGC) survival and preservation of vision and photoreceptors in treated animals compared to controls.
- A single intravitreal delivery of NP-trophic factors provided neuroprotection in animal models of retinal degeneration.
Conclusions:
- Nanoparticle-formulated neurotrophic factors are effective neuroprotective agents in vitro and in vivo.
- Sustained delivery via nanoparticles offers a promising therapeutic approach for progressive retinal degenerative conditions.
- This strategy may benefit patients with retinitis pigmentosa, age-related macular degeneration, and glaucoma.
