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A Tsumura, H Yamada, E Yamada, Y Yamazaki, M Matsumura; Potential Causative Factors for Spontaneous Choroidal Neovascularization in Bst Mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1293.
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Purpose:Bst mice develop spontaneous age-related choroidal neovascularization (CNV). No other animal model for CNV develops CNV spontaneously. Our purpose is to look for the causative factor that leads to the development of CNV in these mice. Methods:Bst mice were purchased commercially from the Jackson Laboratory, and were bred with wild-type C57/bl mice. We selected Bst/+ mice by checking for their short tangled tails and the white coat on their bellies. When the mice were 4 months of age, we performed fluorescein angiography on them and detected fundus vascular abnormalities, including CNV. We repeated the procedure for each animal every 2 months. When we detected mice with CNV, we enucleated the eyeball and processed it for cryo-sectioning. We stained the tissue for CNV by immunohistochemistry using antibodies for vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF2). Results:We examined a total of 20 Bst mice. In 21 eyes out of 40, the fundus appeared normal with a fluorescein angiogram. Among the abnormal eyes, a retinal vascular abnormality with optic disc coloboma was found in 13 eyes (32.5%), massive primary hyaloidal vessel hypertrophy was found in 3 eyes (7.5%), optic disc coloboma without retinal or hyaloidal vessel abnormality was found in 2 eyes (5%), and CNV was found in one eye (2.5%). Light microscopy of the eye with CNV revealed that the CNV was located at the edge of the optic disc coloboma. Immunohistochemistry of the CNV showed intense staining of VEGF and FGF2 in the vascular endothelium while control slidesstained negatively. Conclusion:Although the incidence of CNV in the Bst mice was low, 48% of the total showed some abnormal structure of the fundus. The location of CNV in the Bst mouse looked very similar to the neovascular maculopathy in excessive myopia or CNV associated with optic coloboma in human eyes. Similar to the CNV from surgically excised human specimens, the CNV in the Bst mouse was positive for VEGF and FGF2. These two growth factors could be the cause of spontaneous development of CNV in Bst mice.
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