Abstract
Age-related macular degeneration (AMD) is a multifactorial disease, which can culminate in irreversible vision loss and blindness in elderly. Nowadays, there is a big gap between dry AMD and wet AMD on treatment. Accounting for nearly 90% of AMD, dry AMD still lacks effective treatment. Numerous genetic and molecular researches have confirmed the significant role of the complement system in the pathogenesis of AMD, leading to a deeper exploration of complement inhibitors in the treatment of AMD. To date, at least 14 different complement inhibitors have been or are being explored in AMD in almost 40 clinical trials. While most complement inhibitors fail to treat AMD successfully, two of them are effective in inhibiting the rate of GA progression in phase II clinical trials, and both of them successfully entered phase III trials. Furthermore, recently emerging complement gene therapy and combination therapy also offer new opportunities to treat AMD in the future. In this review, we aim to introduce genetic and molecular associations between the complement system and AMD, provide the updated progress in complement inhibitors in AMD on clinical trials, and discuss the challenges and prospects of complement therapeutic strategies in AMD.
Highlights
Age-related macular degeneration (AMD) is a significant cause of irreversible blindness and vision impairment among the elderly in developed countries [1, 2]
Accounting for about 90% of AMD [5], dry AMD will give rise to macular atrophy and progressive vision loss, featuring photoreceptors, retinal pigment epithelium, and choroidal capillary degeneration, which can be referred to geographic atrophy (GA) as well [6]
On the one hand, these findings suggest that genetic variants that hinder the negative regulation of the complement system promote the development of AMD
Summary
Age-related macular degeneration (AMD) is a significant cause of irreversible blindness and vision impairment among the elderly in developed countries [1, 2]. Wet AMD, known as neovascular AMD, is characterized by a rapid and substantial vision loss, which is caused by the formation of macular neovascularization. Edema, and scar formation of retinal tissue, advanced wet AMD occurs partly due to the upregulation of vascular endothelial growth factor (VEGF). Accounting for about 90% of AMD [5], dry AMD will give rise to macular atrophy and progressive vision loss, featuring photoreceptors, retinal pigment epithelium, and choroidal capillary degeneration, which can be referred to geographic atrophy (GA) as well [6]
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