Abstract
Purpose: :
Subretinal neovascularization (SRN) is a significant feature of VLDL receptor knockout mice (vldlr–/–). We have previously studied the development of SRN, localized VLDLR expression in mouse retina, and examined the mRNA levels of angiogenic factors in vldlr–/– mice. To further characterize the nature of the pathological angiogenic process, various markers were used to determine which cells were activated during the development of SRN in the vldlr–/– mouse.
Methods: :
SRN was examined with ophthalmoscopy, fundus photography, fluorescent angiography, and histology at the ages of 2 weeks through 12 months. Various antibodies including markers for activated macrophage, CD11b, and fibroblast, vimentin, were utilized for immunocytochemistry on retina of age–matched wildtype and vldlr–/– mice.
Results: :
We found that SRN in vldlr–/– retina began to grow at around 3 weeks, peaked at 4 months, and started to decrease at 8 months of age. Findings from fluorescein angiography were consistent with these observations. The fluorescent leakage was hardly seen at 12 months of age when the fundus was full of scattered, depigmented areas. Histological examination revealed that numerous SRNs were still present at older age; however vascular lumen was often absent, and the RPE layer was disrupted around the SRN sites with significant retinal–choroidal anastomoses. Vimentin immunopositive fibroblasts were identified at SRN sites at 3, 6, 8 and 12 months of age with prominent staining in older animals. Activated macrophages were detected at SRN sites at 5 weeks of age, but not at 12 months of age.
Conclusions: :
These results show that fibrosis develops with SRN in vldlr–/– mouse and progresses with age, and the reduced fluorescent leakage in old age is probably due to fibrotic transformation of SRN. Macrophage activation may be involved in the development of SRN in early age of the vldlr–/– mice.
Keywords: retinal neovascularization