COCO/DAND5 inhibits developmental and pathological ocular angiogenesis

Area of Science:

• Ophthalmology
• Molecular Biology
• Angiogenesis Research

Background:

• Neovascularization drives visual disorders such as age-related macular degeneration (AMD) and retinopathy of prematurity.
• Current treatments target vascular endothelial growth factor (VEGF), but resistance and side effects like geographic atrophy are concerns.
• Alternative therapeutic pathways for ocular angiogenesis are crucial.

Purpose of the Study:

• To identify and characterize a novel inhibitor of pathological ocular angiogenesis.
• To evaluate the therapeutic potential of COCO in preclinical models of neovascular eye diseases.

Main Methods:

• In vitro assessment of COCO's effects on endothelial cell proliferation, migration, and sprouting.
• In vivo studies using intravitreal injections of COCO in models of retinopathy of prematurity and choroidal neovascularization.
• Mechanistic studies investigating COCO's impact on TGFβ, BMP pathways, cellular metabolism, and redox balance.

Main Results:

• COCO significantly inhibited endothelial cell sprouting, migration, and proliferation in vitro.
• Intravitreal COCO administration suppressed retinal vascularization in developmental and retinopathy of prematurity models.
• COCO effectively reduced angiogenesis in choroidal neovascularization models.
• Mechanistically, COCO modulated TGFβ and BMP signaling, altered cellular energy metabolism, and affected redox balance.

Conclusions:

• COCO is a potent inhibitor of both retinal and choroidal angiogenesis.
• COCO presents a promising therapeutic candidate for neovascular ocular diseases, addressing limitations of current anti-VEGF therapies.