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D. Skondra, H.J. Zambarakji, T. Nakazawa, E. Connolly, K. Thomas, A.–M. Lane, E.S. Gragoudas, J.W. Miller, A. Hafezi–Moghadam; Blood Retina Barrier Function and Angiogenesis in Apolipoprotein E Deficient Mice . Invest. Ophthalmol. Vis. Sci. 2005;46(13):448.
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Purpose:Apolipoprotein E (apoE) has been implicated in angiogenesis and vascular permeability. We investigated the role of this molecule in the integrity of the Blood Retina Barrier (BRB) and choroidal neovascularization (CNV) in combination with high plasma cholesterol levels. Methods: BRB permeability was quantified using the Evans Blue (EB) technique in 12–16 week old apoE deficient (apoE–/–) mice on normal chow diet (ND) (n=11) and in age matched normal wild–type mice (WT) on the same genetic background (C57Bl6/J mice) (n=12). To achieve higher cholesterol levels, apoE–/– mice were fed with a Western–type diet (WD) for 6 weeks (n=5). Plasma cholesterol levels were measured before and at the end of the 6 week period of WD. CNV was induced with a 532 nm laser (4 spots, size 50µm, energy 200mW, duration 0.1 sec) in 11–16 week old apoE–/– mice on WD diet (n=5), apoE–/– mice on ND (n=8), as well as in age–matched WT (n=6). The extent of the CNV in the different groups was graded by fluorescein angiography (FA) by 2 masked observers, 14 days after the laser–induced injury, using grading standards. Results:ApoE–/– mice on ND showed a trend to higher BRB leakage compared to WT, using the Evans Blue technique. However, our preliminary experiments do not reach statistical significance (5.61± 0.82 vs. 4.47± 0.39, P>0.05). The leakage from the neovascular membranes of apoE–/– mice on WD, apoE–/– mice on ND, and WT mice were not statistically different (Fisher’s exact test, p = 0.81), even though the cholesterol levels were significantly higher in apoE–/– mice after 6 weeks of WD compared to their baseline levels (554.8 ±34.5 mg/dl vs. 351.6 ±27.3, P=0.013). Conclusions:In this study, young (12–16 week old) apoE–/– mice on ND showed a trend to a higher BRB permeability. This suggests that this protein may play a role in the integrity of retinal vessels. ApoE deficiency alone or in combination with an increased plasma cholesterol level does not appear to make mice in this age group more prone to CNV. This suggests that apoE may not be a sole regulator of CNV formation in younger animals. Further studies with older mice will be performed to address a potential role for apoE and higher plasma cholesterol levels in ocular angiogenesis.
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