Emerging roles for the CD36 scavenger receptor as a potential therapeutic target for corneal neovascularization.
Neovascularization (NV) of the normally avascular cornea arises from various causes including inflammation, infection, trauma, and contact lens wear. Corneal NV, whatever the cause, impairs vision and threatens the survival of corneal allografts, thus representing a serious clinical problem for which treatment is limited. Recent interest has focused on vascular endothelial growth factor (VEGF), a key angiogenic factor whose role in corneal NV is amply documented. While experimental studies underscore the efficacy of anti-VEGF targeted agents, there exists no clear consensus on the ideal treatment for this multifaceted pathology. This review discusses the therapeutic potential of CD36, a well established anti-angiogenic receptor. We present evidence that CD36 contributes significantly to the maintenance of corneal avascularity wherein its deficiency leads to age-related corneal NV. Data further reveal that activation of CD36 substantially attenuates and induces regression of inflammatory corneal NV via concerted inhibition of VEGFA, c-Jun N terminal kinase-1, and c-Jun. In parallel studies, we demonstrate that hypoxia, a fundamental stimulus of NV, markedly elevates CD36 corneal expression in a hypoxia-inducible factor-1 and reactive oxygen species dependent manner. Collectively, our findings unveil interesting avenues for future research on the involvement of CD36 in neovascular eye disease and suggest CD36 agonists as potential therapeutic agents for the management of corneal NV, possibly in combination with anti-VEGF therapies.
Mwaikambo
B R
BR
Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada . pierre.hardy@recherche-ste-justine.qc.ca
Yang
C
C
Ong
H
H
Chemtob
S
S
Hardy
P
P
D042501:Angiogenic Proteins / Q000502:physiology; D000818:Animals; D018955:CD36 Antigens / Q000187:drug effects* / Q000502:physiology*; D003315:Cornea / Q000098:blood supply / Q000473:pathology; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D012039:Regional Blood Flow / Q000502:physiology
D042501:Angiogenic Proteins; D018955:CD36 Antigens