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Identifying a novel retinal pigment epithelium specific adeno-associated virus vector

ABSTRACT: Retinal Pigment Epithelium (RPE) are crucial for maintaining retinal homeostasis and the visual cycle. Currently, there are no effective treatments for blinding retinal diseases caused by RPE cell degeneration. Gene therapy presents a promising approach, but no gene therapy vectors specifically targeting RPE cells are available. In this study, we utilized an AAV2 random mutation library and high-throughput sequencing to screen AAV vectors （AAV206）capable of specifically targeting RPE cells. Intravitreal injection of the AAV206 vector in mice demonstrated that AAV206 specifically infected RPE cells, whereas AAV2 primarily infects the inner retina. Furthermore, AAV206 exhibited lower immunogenicity and toxicity compared to AAV2. Overexpression of sFLT-1 through AAV206 effectively inhibited the size and leakage of choroidal neovascularization. In summary, AAV206 is an ideal vector for gene therapy targeting RPE cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE271661 | GEO | 2025/01/29

REPOSITORIES: GEO

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In vivo Gene Expression Profiling of RPE/choroid Post-Intravitreal Injections of Dexamethasone and Triamcinolone at Clinically Relevant Time Points for Patient Care

Project description:PURPOSE To identify retinal pigment epithelial (RPE)/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. METHODS Differential gene expression of over 34,000 well-characterized mouse genes, in the RPE/choroid of 6 week old C57BL/6J mice were analyzed after intravitreal steroid injections at 1 week and 1 month post injection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpringGX12.5 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. RESULTS Both triamcinolone and dexamethasone caused differential activation of genes involved in ‘Circadian Rhythm Signaling’ pathway at both time points tested. Triamcinolone (TAA) uniquely induced significant changes in gene expression in ‘Calcium Signaling’ (1 week) and ‘Glutamate Signaling’ pathways (1month). In contrast, Dexamethasone (Dex) affected the ‘GABA Receptor Signaling’ (1 week) and ‘Serotonin Receptor Signaling’ (1month) pathways. CONCLUSIONS Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid cells during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina.

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