ArticleInvestigative ophthalmology & visual science2025
Targeted Neuroprotection of Retinal Ganglion Cells Via AAV2-hSyn-NGF Gene Therapy in Glaucoma Models.
Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- The Dual Role of Macroglia in Glaucoma: Deciphering the Contributions of Astrocytes and Müller Cells to Retinal Neurodegeneration and Neuroprotection.International journal of molecular sciences · 2026Review
- A Phase I Randomized Trial of Topical Insulin for Glaucoma: Safety and Efficacy Outcomes.Ophthalmology science · 2026Article
- The controversial role of nutraceuticals vs. drugs in proliferative retinopathies.Frontiers in neuroscience · 2025Review
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: The purpose of this study was to evaluate the neuroprotective effects of delivering nerve growth factor (NGF) to retinal ganglion cells (RGCs) through adeno-associated virus serotype 2 (AAV2) carrying a neuronal-specific human synapsin (hSyn) promoter. Methods: AAV2-hSyn-NGF was injected intravitreally in three glaucoma models: optic nerve crush (ONC), microbead-induced ocular hypertension (MB), and genetic glaucoma model (DBA). Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) determined the optimal injection concentration of AAV vector. Flow cytometry monitored immune responses. Transduction efficiency was quantified using green fluorescent protein (GFP) co-localization with RGC-specific marker RNA-binding protein with multiple splicing (RBPMS). The RGCs' density, retinal nerve fiber density, ganglion cell complex thickness, and positive scotopic threshold response (pSTR) were measured to assess structural and functional outcomes of the RGCs. Non-parametric Mann-Whitney U tests or Kruskal-Wallis tests were utilized to ascertain the statistical significance (P < 0.05). Results: The optimal concentration of AAV vector for intravitreal injection was determined to be 1 × 1010 vector particles (VPs) per eye. The use of the hSyn promoter significantly enhanced targeting specificity to RGCs, resulting in a transduction efficiency of 46.64% ± 2.18%. Administration of AAV2-hSyn-NGF effectively preserved the RGCs' density, nerve fiber layer integrity, and the thickness of ganglion cell complex, while maintaining the RGCs' function across three glaucoma models. Furthermore, this gene delivery system did not elicit detectable immune responses or structural damage to the retina. Conclusions: The AAV2-hSyn-NGF gene therapy offers a safe and effective neuroprotective strategy for RGCs across multiple glaucoma models, making it a promising candidate for future clinical trials in patients with glaucoma.
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