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Updated: Aug 22, 2025
Using Adeno-associated Virus as a Tool to Study Retinal Barriers in Disease
Published on: April 19, 2015
Transcriptome analysis of AAV-induced retinopathy models expressing human VEGF, TNF-α, and IL-6 in murine eyes
Kolja Becker1, Carina M Weigelt2, Holger Fuchs2
1Global Computational Biology & Digital Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany. Kolja.becker@boehringer-ingelheim.com.
Abstract:
Retinopathies are multifactorial diseases with complex pathologies that eventually lead to vision loss. Animal models facilitate the understanding of the pathophysiology and identification of novel treatment options. However, each animal model reflects only specific disease aspects and understanding of the specific molecular changes in most disease models is limited. Here, we conducted transcriptome analysis of murine ocular tissue transduced with recombinant Adeno-associated viruses (AAVs) expressing either human VEGF-A, TNF-α, or IL-6. VEGF expression led to a distinct regulation of extracellular matrix (ECM)-associated genes. In contrast, both TNF-α and IL-6 led to more comparable gene expression changes in interleukin signaling, and the complement cascade, with TNF-α-induced changes being more pronounced. Furthermore, integration of single cell RNA-Sequencing data suggested an increase of endothelial cell-specific marker genes by VEGF, while TNF-α expression increased the expression T-cell markers. Both TNF-α and IL-6 expression led to an increase in macrophage markers. Finally, transcriptomic changes in AAV-VEGF treated mice largely overlapped with gene expression changes observed in the oxygen-induced retinopathy model, especially regarding ECM components and endothelial cell-specific gene expression. Altogether, our study represents a valuable investigation of gene expression changes induced by VEGF, TNF-α, and IL-6 and will aid researchers in selecting appropriate animal models for retinopathies based on their agreement with the human pathophysiology.
Insights
This study analyzed gene expression changes in mouse eyes after introducing VEGF-A, TNF-α, or IL-6 using Adeno-associated viruses (AAVs). Findings help select better animal models for retinopathy research by comparing molecular changes.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genomics
Background:
- Retinopathies are complex diseases causing vision loss, necessitating effective animal models for research.
- Existing animal models for retinopathies offer limited insights into specific molecular pathologies.
- Understanding molecular changes in disease models is crucial for developing novel treatments.
Purpose of the Study:
- To investigate the molecular changes induced by specific gene expressions (VEGF-A, TNF-α, IL-6) in ocular tissues using Adeno-associated virus (AAV) vectors.
- To compare the transcriptomic profiles resulting from these gene expressions with established retinopathy models.
- To provide guidance for selecting appropriate animal models for retinopathy research based on molecular mimicry.
Main Methods:
- Transcriptome analysis of murine ocular tissues transduced with recombinant Adeno-associated viruses (AAVs) expressing VEGF-A, TNF-α, or IL-6.
- Integration of single-cell RNA sequencing data to identify cell-type-specific gene expression changes.
- Comparative analysis of gene expression profiles with data from the oxygen-induced retinopathy model.
Main Results:
- VEGF-A expression distinctly regulated extracellular matrix (ECM)-associated genes and increased endothelial cell markers.
- TNF-α and IL-6 induced comparable changes in interleukin signaling and complement cascade, with TNF-α effects being more pronounced.
- Both TNF-α and IL-6 increased macrophage markers, while TNF-α also increased T-cell markers.
- Transcriptomic changes in AAV-VEGF treated mice significantly overlapped with the oxygen-induced retinopathy model, particularly in ECM and endothelial gene expression.
Conclusions:
- Adeno-associated virus (AAV)-mediated expression of VEGF-A, TNF-α, and IL-6 induces distinct transcriptomic changes in ocular tissues.
- The study highlights the utility of AAV-based gene expression for modeling specific aspects of retinopathy pathophysiology.
- Findings aid researchers in selecting more relevant animal models for retinopathies by aligning molecular signatures with human disease.
