Abstract
Abstract: :
Purpose: From ENU–induced new ocular mutants, we identified two recessive mutations BEMr18 (r18) and BEMr26 (r26), with retinal ischemia and neovascularization respectively. We have mapped the chromosomal locations of both mutations and investigated their retinal phenotypes in compared to that of VLDL receptor null mice. Methods: Chromosomal location was determined by genome–wide linkage analysis of the mice generated between strains C57BL/6J and C3H. Their retinal phenotypes were examined by indirect ophthalmoscope, fluorescein angiogram, electroretinogram (ERG), histopathology, immunocytochemistry, western blotting, and thin–sectional electron microscopic analysis. Results: r18 and r26 were identified from ENU–induced F3 mice. Their homozygous mice were fertile. Angiogram data showed profound leaking spots matching to the yellow spots on its Fundus. Histopathology showed cell growth from inner retinal layers to subretinal space. The outer segments of photoreceptor cells, next to these abnormal cells in the subretinal space, were completely degenerated. Some of the cells in the subretinal space were immuno–positive for CD31 or alpha smooth muscle actin. The phenotypes of r26 were similar to retinal neovascularization of VLDLR –/– mice. However, Angiogram data of r18 showed a homogenous vascular leakage of the retina with a progressive of ischemic regions. CD31 labeling verified a loss of the vessels in the outer plexiform layer. ERG showed a reduction of the B–wave, but not the A–wave. Both mutations were mapped to Chr 19, lod scores 4.7 for r26 and 4.6 for r18. Conclusions: r26 and r18 are new mutations for retinal neovascularization and ischemia respectively. The pair of mutations represent two essential features, overgrowth or reduction, of the retinal vasculature. Moreover, their phenotypes appeared to be similar to alterations of retinal vessels in proliferative or non–proliferative diabetic retinopathy. Further studies of both mutations may lead to molecular insights for the developmental and pathological regulation of retinal vasculature.
Keywords: diabetic retinopathy • retinal neovascularization • ischemia