Genetic ablation of CD36 induces age-related corneal neovascularization.
OBJECTIVE
Corneal avascularity is tightly regulated by a balance between angiogenic and antiangiogenic factors (angiogenic privilege). In the current study, we tested the hypothesis that the CD36+/+ antiangiogenic receptor contributes toward the maintenance of corneal avascularity.


METHODS
Corneas of CD36 wild-type (CD36) and knockout (CD36) mice aged 4, 16, 52, and 78 weeks were histologically evaluated for corneal haze and neovascularization (NV). Quantitative real-time polymerase chain reaction was performed on corneal tissue from CD36+/+ and CD36-/- mice aged 4 and 52 weeks to examine the effect of CD36 deficiency on expression of relevant angiogenic factors.


RESULTS
Corneal haze and NV were absent in CD36+/+ mice at all ages. Conversely, corneal haze and NV were evident at 52 and 78 weeks in CD36-/- mice, and the latter demonstrated a significant increase in vessel density at 52 and 78 weeks. Interestingly, compared with CD36+/+ mice, in the corneas of 52-week-old CD36-/- mice, thrombospondin-1 messenger RNA was repressed, and vascular endothelial growth factor A, c-Jun N-terminal kinase-1, and c-Jun levels were robustly upregulated.


CONCLUSIONS
CD36-/- mice develop corneal NV that increases in severity with age, thus accentuating the role of CD36 in preserving corneal avascularity.
Mwaikambo
Bupe R
BR
Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada.
Sennlaub
Florian
F
Ong
Huy
H
Chemtob
Sylvain
S
Hardy
Pierre
P
D000375:Aging; D000818:Animals; D001808:Blood Vessels / Q000473:pathology; D018955:CD36 Antigens / Q000235:genetics*; D003315:Cornea / Q000098:blood supply / Q000378:metabolism; D016510:Corneal Neovascularization / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003318:Corneal Opacity / Q000209:etiology; D015536:Down-Regulation; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019700:Thrombospondin 1 / Q000235:genetics; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018955:CD36 Antigens; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D048055:Mitogen-Activated Protein Kinase 8