Abstract
Purpose: :
The maintenance of corneal avascularity is essential to vision. D6 is a promiscuous decoy receptor that scavenges CC chemokines and plays a non-redundant role in regulation of inflammatory responses in various organs. As inflammation is a key player in corneal angiogenesis, we hypothesized that D6 expression plays a role in controlling inflammation and corneal vessel formation.
Methods: :
Corneal inflammation and angiogenesis were induced using the corneal micro-pocket assay with basic fibroblast growth factor (b-FGF) pellets in the mouse. Expression of chemokines in the cornea were analyzed in D6 -/-, and wild type following pellet implantation. Infiltration of CD45+ leukocyte cells into the cornea was evaluated by flow cytormetry. Additionally, angiogenesis was quantified by double immunofluorescence staining of corneal flat mounts for blood vessels (CD31high, LYVE-1-), and lymphatic vessels (CD31low, LYVE-1+) and calculated as a percentage of the total corneal area.
Results: :
One week after corneal micropellet implantation, the corneas of D6 -/- mice were associated with increased levels for inflammatory chemokines CCL2, CCL3, and CCL5, whereas CXCL9 was not different between knockout and wild-type mice. D6 -/- mice had a significantly (50%) higher infiltration of leukocytes into the cornea detected by flow cytometry 3 days post-surgery. Moreover, blood vessels (33.2%; p<0.01) and lymphatic growth (25.1%; p<0.05) into the cornea were significantly higher in D6 -/- compared to the wild-type.
Conclusions: :
Our data suggest that D6 plays a role in controlling corneal inflammation and angiogenesis. These results support the importance of chemokine regulation through D6 in corneal angiogenesis and describe a new mechanism of immune modulation within the cornea.
Keywords: immunomodulation/immunoregulation • neovascularization