Abstract
Purpose: :
Some mouse strains such as C57BL6 (pigmented) respond to hyperoxia-induced vaso-obliteration by developing pathological neovascularization (oxygen-induced retinopathy, OIR), whereas others such as FVB (albino) heal by healthy vessel regeneration. It has been suggested that pigmentation and/or melanin may play a role in OIR in rats. In order to test this link in mice, and to further understand the inheritance susceptibility of OIR in C57BL6 and FVB we used backcross analysis between the two strains.
Methods: :
First (F1) and second generation (F2) offspring from FVB and C57BL6 crosses were exposed to 75% oxygen at P7 for 5 days. Retinal avascular area and pathological neovascularization was analysed at P17 by immunohistochemistry. Expression of Vegf mRNA in retinas was quantified by quantitative PCR.
Results: :
In the F1 generation (agouti coat colour) all pups showed aggressive pathological neovascularization. In F2 crosses, only about 75% showed this while the rest regenerated in a normal fashion by P17. Association with pigmentation was lost in the F2 generation. Vegf mRNA levels at P13 and P15 was similar to controls in FVB but significantly higher in C57BL6 mice.
Conclusions: :
In crosses between the C57Bl6 and the FVB strain susceptibility to pathological neovascularization in OIR is inherited in autosomal dominant fashion, whereas healthy retinal vasculature regeneration follows an autosomal recessive pattern of inheritance. Lack of association with pigmentation suggests that melanin does not influence pathological neovascularization in this genetic background. However, association of high Vegf expression with neovascularization suggests that genetic differences may influence susceptibility to neovascularization via Vegf expression levels.
Keywords: neovascularization • regeneration • ischemia