ArticleInvestigative ophthalmology & visual science2026
Neuritin1 Cis-Regulatory Elements Enable Gene Expression Preferentially in Retinal Ganglion Cells.
Article in Investigative ophthalmology & visual science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Corrections and comments
- Update ofNeuritin12026
Authors and funding
6 authors.
Funding
Abstract
Purpose: Retinal ganglion cells (RGCs) are essential for visual signal transmission, yet they are vulnerable to injury and degeneration. Gene modulation in RGCs using adeno-associated virus (AAV) offers a promising avenue for neuroprotection and regeneration, but promoters lack sufficient RGC specificity, limiting the precision needed for preclinical studies. This study aims to identify novel promoter-enhancer combinations (PECs) to achieve gene expression preferentially in RGCs. Methods: We evaluated existing transcriptomic data to identify neuritin 1 (Nrn1) as a gene with highly restricted RGC expression in the retina. Synthetic PECs derived from human and mouse Nrn1 loci were incorporated into AAV2 vectors driving expression of a nuclear-targeted reporter GreenLantern. AAVs were delivered via intravitreal injection into C57BL6/J mice, and transduction efficiency and RGC specificity were evaluated in both young and aged retinas and those subjected to intraorbital optic nerve crush (ONC), using immunohistochemistry and quantitative analysis of RBPMS+ cells. Results: We found that AAV2 with a human Nrn1-PEC drives gene expression in RGCs. Quantitative analysis revealed that over 83% of transduced cells were RBPMS+, indicating robust RGC selectivity and significantly outperforming ubiquitous promoters. Notably, the Nrn1-PEC retained strong and selective transgene expression in RGCs in aged mice and following ONC, demonstrating its resilience under aged and injury conditions. Conclusions: The Nrn1-PEC enables efficient and injury-resilient gene expression in RGCs, addressing a key limitation in cell-specific targeting. This AAV-incorporated PEC offers a robust platform for evaluating neuroprotective interventions and accelerates the translational development of gene therapies for glaucoma and other optic neuropathies.
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