MAR 20, 2013
This study conducted in mice examined spatial variances in ligand expression and angiogenic effect in response to the inflammatory response induced by basic fibroblast growth factor (b-FGF). The results indicate that b-FGF may simultaneously provoke hemangiogenesis and lymphangiogenesis in different locations of the cornea through differential expression of vascular endothelial growth factor (VEGF) ligands. The authors report in the July issue of Cornea that this suggests the existence of global changes in corneal immunity and predilection for inflammation beyond what can be seen by slit lamp examination.
They implanted b-FGF micropellets (80 ng) in the temporal side of the cornea of Balb/c mice. On days 1, 3 and 7, they observed blood (heme-) and lymphangiogenesis by immunofluorescence staining of corneal flat mounts to identify lymphatic and blood vessels, respectively.
A second group of corneas were harvested for quantitative real-time polymerase chain reaction (PCR). Each cornea was divided into two areas: pre-pellet area (PA) or temporal cornea, and opposite-pellet area (OA) or the nasal part of the cornea. Expression of VEGF ligands was evaluated using real-time PCR in each zone.
They found that blood vessels grew into the cornea from the PA, whereas corneal lymphatic vessels grew from the OA toward the center of the cornea. VEGF-A was upregulated in the PA, whereas VEGF-D expression was mostly observed in the OA. VEGF-C level increased simultaneously in both areas.
The authors say the novel finding in this study is the high lymphangiogenic response noted after b-FGF stimulation in the cornea on the opposite side from where the FGF pellet is implanted. These results imply that continued induction of immune reactivity could be ongoing, away from the site of inflammation even when the therapy has led to blood vessel regression. They say that inflammatory changes that induce even sectoral corneal angiogenesis likely lead to more "global" changes in corneal immunity.
Their data imply that assessment of corneal lymphatics using in vivo imaging technologies should include the area opposite the site of inflammation.