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E. Chung, D. R. Saban, R. Dana; Development of Two Distinct and Novel Recipient Models for High-Risk Corneal Transplantation: Blood Vessel- versus Lymphatic Vessel- Dominance. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1475. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To develop novel recipient bed models for high-risk corneal transplantation with blood vessel- versus lymphatic vessel-dominance.
To characterize the angiogenic phenotype of b-FGF in disparate doses at varying time points, we implanted high (80ng) and low dose (12.5ng) b-FGF pellets into BALB/c mouse corneas. Angiogenic responses were analyzed by immunohistochemistry by quantifying blood neovessels (CD31hi/LYVE-1- ) or lymphatic neovessels (CD31low/LYVE-1hi) out to 3 weeks post-pellet implantation. The area covered by blood neovessels (BV) and lymph neovessels (LV) were calculated (NIH Image software J 1.34) and expressed as % of total corneal area. The ‘Relative LV’ (RLV) was calculated using equation: RLV (%) = LV/BV × 100 to dissect the level of lymphatic neovascularization from the total angiogenic response. To test the suppressive effect of angiogenesis, we evaluated the inhibitory effect of selective blocking of VEGFR-2 or VEGFR-3 on hemangiogenesis (HA) and lymphangiogenesis (LA).
Although, high-dose b-FGF stimulation induced a stronger angiogenic response, the RLV values were relatively identical in high- and low-doses. Delayed LA response induced at 3 weeks post-implantation of high dose b-FGF resulted in formation of a typical angiogenic phenotype with lymphatic vessel dominance. In comparison to significant suppression of both %BV and %LV by VEGFR-2 blockade, anti-VEGFR-3 antibody inhibited only %LV (p=0.0002) with no concurrent inhibition of %BV (p=0.79) and formed characteristic angiogenic phenotype with blood vessel dominance.
An "HA-dominant" corneal phenotype can be obtained in BALB/c mice 2 weeks post-implantation of an 80ng b-FGF micropellet and VEGFR-3 blockade. Alternatively, an "LA-dominant" corneal phenotype can be obtained 3 weeks post-implantation of an 80ng b-FGF micropellet, without supplementary modulating agents
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