Emerging Roles for the CD36 Scavenger Receptor as a Potential Therapeutic Target for Corneal Neovascularization

Abstract

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.

The thrombospondin-1 receptor CD36 is an important mediator of ovarian angiogenesis and folliculogenesis

“…CD36 appears to be critical in the regulation of physiological and pathophysiological angiogenesis. CD36 mediated TSP-1 signaling maintains corneal vascularity and CD36 deficiency leads to age-related corneal neovascularization while activation of CD36 can induce regression of inflammatory corneal angiogenesis [ 38 ]. CD36 has been implicated in the regulation of tumor angiogenesis.…”

Corneal Neovascularization: An Anti-VEGF Therapy Review

“…138 Other molecules that have demonstrated inhibitory effects on corneal neovascularization include suleparoide, thalidomide, suramin, genistein, somatostatin, octreotide, and rapamycin. 115 More recent work has implicated CD36 (an antiangiogenic receptor), brain-specific angiogenesis inhibitor 1, suramab, propolis extract, and various nutrient mixtures as having the capability to reduce corneal neovascularization, 74,86,96,97,116,137 and revealed that the network of molecules involved in corneal angiogenesis is even more extensive than what was previously thought to be. Many of these have been shown to reduce angiogenesis in part by reducing VEGF levels, and some have also shown efficacy in cancer treatment.…”

Influences of Histidine-1 and Azaphenylalanine-4 on the Affinity, Anti-inflammatory, and Antiangiogenic Activities of Azapeptide Cluster of Differentiation 36 Receptor Modulators

“…The cluster of differentiation 36 receptor (CD36) is a glycoprotein expressed in the membranes of various cells, including red blood cells and macrophages. , Classified as a class B scavenger receptor, CD36 acts in normal cellular function by binding to a variety of endogenous ligands, including oxidized low-density lipoproteins and thrombospondin . Moreover, CD36 is coexpressed with the Toll-like receptor-2 (TLR-2)–TLR-6 complex that plays a significant role in innate immunity. , In the light of such interactions, CD36 is a promising therapeutic target for the treatment of various indications including atherosclerosis, angiogenesis, and age-related macular degeneration. − …”