Publications by authors named "Nuala O'Neill"
Article Synopsis
- Adeno-associated virus (AAV) can effectively deliver genes to retinal ganglion cells (RGCs), but there's a limitation due to packaging size and cell selectivity of the therapeutic genes.
- This study evaluates the effectiveness of various RGC-selective promoters, including gamma-synuclein (SNCG) and neurofilament heavy chain (NEFH), alongside parts of the atonal bHLH transcription factor 7 (ATOH7) enhancer.
- Results indicate that both SNCG and NEFH promoters are similarly effective for gene delivery and enhancing RGC survival, but the NEFH promoter has the advantage of a smaller size for packaging, making it more suitable for delivering larger genes in future applications.
Purpose: Retinal ganglion cell (RGC) loss provides the basis for diagnosis and stage determination of many optic neuropathies, and quantification of RGC survival is a critical outcome measure in models of optic neuropathy. This study examines the accuracy of manual RGC counting using two selective markers, Brn3a and RBPMS.
Methods: Retinal flat mounts from 1- to 18-month-old C57BL/6 mice, and from mice after microbead (MB)-induced intraocular pressure (IOP) elevation, are immunostained with Brn3a and/or RBPMS antibodies.
SIRT1 prevents retinal ganglion cell (RGC) loss in several acute and subacute optic neuropathy models following pharmacologic activation or genetic overexpression. We hypothesized that adeno-associated virus (AAV)-mediated overexpression of SIRT1 in RGCs in a chronic ocular hypertension model can reduce RGC loss, thereby preserving visual function by sustained therapeutic effect. A control vector AAV-eGFP and therapeutic vector AAV-SIRT1 were constructed and optimized for transduction efficiency.
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