Artikel
A new animal model for studying angiopoietin-2-dependent angiogenesis in the retina
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Autoren
Veröffentlicht: | 22. September 2004 |
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Gliederung
Text
Objective
Diabetic retinopathy is the leading cause for blindness in people of working age. Pericyte loss is the earliest morphological change in diabetic retinopathy. The Angiopoietin-Tie System plays a pivotal role in this process and retinal Angiopoietin-2 (Ang-2) is upregulated just before the onset of pericyte loss.
Methods
We investigated a transgenic mouse line that overexpresses human angiopoietin-2 under the control of the mouse photoreceptor opsin promoter. To analyse physiological angiogenesis we used lectin-stained retinal whole mount preparations. The role of Ang-2 in pathological angiogenesis was investigated using the ROP model. Proliferative retinopathy is triggered by the hypoxia, which occurs after exposure to 75% Oxygen for five days. Nuclei of neovascularizations were counted on the vitreal side of the inner limiting membrane in PAS stained Paraffin sections.
Results
Analysis of developmental sprouting of the mouse retina revealed a significant increase in the outgrowth of the retinal vasculature in the transgenic mice compared with wild-type littermates. The hypoxiastimulus in the ROP significantly promotes retinal angiogenesis in the transgenic mice compared to wildtype littermates and age-matched controls kept under normoxic conditions.
Conclusions
We conclude that the transgenic mouse line, which overexpresses hAng-2 under the control of mOpsin promoter in the retina, is a suitable mouse model to analyse the function of Ang-2 in retinal angiogenesis. Our experiments confirmed that overexpression of Ang-2 leads to increased angiogenic sprouting in the retina. In further experiments we will study this animal model under diabetic conditions.