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Updated: Jul 6, 2025
Monitoring Dynamic Growth of Retinal Vessels in Oxygen-Induced Retinopathy Mouse Model
Published on: April 2, 2021
Transcriptional Comparison of Human and Murine Retinal Neovascularization
Laurenz Pauleikhoff1,2, Stefaniya Boneva1, Myriam Boeck1,3
1Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Purpose:
Retinal neovascularization (RNV) is the leading cause of vision loss in diseases like proliferative diabetic retinopathy (PDR). A significant failure rate of current treatments indicates the need for novel treatment targets. Animal models are crucial in this process, but current diabetic retinopathy models do not develop RNV. Although the nondiabetic oxygen-induced retinopathy (OIR) mouse model is used to study RNV development, it is largely unknown how closely it resembles human PDR.
Methods:
We therefore performed RNA sequencing on murine (C57BL/6J) OIR retinas (n = 14) and human PDR RNV membranes (n = 7) extracted during vitrectomy, each with reference to control tissue (n=13/10). Differentially expressed genes (DEG) and associated biological processes were analyzed and compared between human and murine RNV to assess molecular overlap and identify phylogenetically conserved factors.
Results:
In total, 213 murine- and 1223 human-specific factors were upregulated with a small overlap of 94 DEG (7% of human DEG), although similar biological processes such as angiogenesis, regulation of immune response, and extracellular matrix organization were activated in both species. Phylogenetically conserved mediators included ANGPT2, S100A8, MCAM, EDNRA, and CCR7.
Conclusions:
Even though few individual genes were upregulated simultaneously in both species, similar biological processes appeared to be activated. These findings demonstrate the potential and limitations of the OIR model to study human PDR and identify phylogenetically conserved potential treatment targets for PDR.
Insights
The oxygen-induced retinopathy (OIR) mouse model partially mimics human proliferative diabetic retinopathy (PDR) by activating similar biological pathways, despite limited gene overlap. This suggests conserved targets for PDR treatment.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genomics
Background:
- Retinal neovascularization (RNV) causes vision loss in proliferative diabetic retinopathy (PDR).
- Current PDR treatments have high failure rates, necessitating new therapeutic targets.
- Existing diabetic retinopathy animal models do not develop RNV, limiting research.
Purpose of the Study:
- To compare gene expression profiles between the oxygen-induced retinopathy (OIR) mouse model and human PDR RNV membranes.
- To assess the molecular similarity and identify conserved factors between the OIR model and human PDR.
- To evaluate the OIR model's suitability for studying human PDR.
Main Methods:
- RNA sequencing was performed on murine OIR retinas and human PDR RNV membranes.
- Differential gene expression (DEG) analysis was conducted comparing RNV tissue to controls.
- Biological processes and phylogenetically conserved factors were identified and compared between species.
Main Results:
- 213 murine and 1223 human specific upregulated factors were identified.
- A small overlap of 94 DEG (7% of human DEG) was observed between species.
- Similar biological processes, including angiogenesis and immune response regulation, were activated in both OIR and PDR.
Conclusions:
- Despite limited individual gene overlap, the OIR model activates conserved biological pathways relevant to human PDR.
- The OIR model has both potential and limitations for studying human PDR.
- Conserved factors like ANGPT2, S100A8, MCAM, EDNRA, and CCR7 represent potential therapeutic targets for PDR.
