The Role of Inflammation in Age-Related Macular Degeneration—Therapeutic Landscapes in Geographic Atrophy

Abstract

Age-related macular degeneration (AMD) is the leading cause of vision loss and visual impairment in people over 50 years of age. In the current therapeutic landscape, intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies have been central to the management of neovascular AMD (also known as wet AMD), whereas treatments for geographic atrophy have lagged behind. Several therapeutic approaches are being developed for geographic atrophy with the goal of either slowing down disease progression or reversing sight loss. Such strategies target the inflammatory pathways, complement cascade, visual cycle or neuroprotective mechanisms to slow down the degeneration. In addition, retinal implants have been tried for vision restoration and stem cell therapies for potentially a dual purpose of slowing down the degeneration and restoring visual function. In particular, therapies focusing on the complement pathway have shown promising results with the FDA approved pegcetacoplan, a complement C3 inhibitor, and avacincaptad pegol, a complement C5 inhibitor. In this review, we discuss the mechanisms of inflammation in AMD and outline the therapeutic landscapes of atrophy AMD. Improved understanding of the various pathway components and their interplay in this complex neuroinflammatory degeneration will guide the development of current and future therapeutic options, such as optogenetic therapy.

Immune System, Inflammation and Autoantigens in Wet Age-Related Macular Degeneration: Pathological Significance and Therapeutic Importance

“…When the cycle of retinal injury and repair continues unabated, the resident immune cells require support from the systemic immune cells in a similar manner to that reported in neurodegenerative diseases by Schwartz and Shechter in 2010 [30]. If the retinal injuries/damage become persistent such that the resident immune cells become exhausted and sustained systemic support is required, this eventually may Currently, there is no cure for early or dAMD and associated conditions; however, recently, pegcetacoplan (Syfovre) and avacincaptad pegol (Izervay) administered intravitreally were approved by the FDA for the treatment of GA [14,15]. The mainstay therapy for wAMD is anti-vascular endothelial growth factor (anti-VEGF) therapy.…”

“…Life 2023, 13,2236 2 of 12 metabolic waste/deposits, and death of PR and RPE, which can progress to chronic disease states such as wAMD, geographic atrophy (GA), or subretinal fibrosis [4][5][6][7][8][9][10][11][12][13]. Currently, there is no cure for early or dAMD and associated conditions; however, recently, pegcetacoplan (Syfovre) and avacincaptad pegol (Izervay) administered intravitreally were approved by the FDA for the treatment of GA [14,15]. The mainstay therapy for wAMD is anti-vascular endothelial growth factor (anti-VEGF) therapy.…”

Recent Advances in Our Understanding of Age-Related Macular Degeneration: Mitochondrial Dysfunction, Redox Signaling, and the Complement System

“…An excess of ROS can adversely affect complement functionality in various ways [315]. Chen et al demonstrated in cultured RPE cells from mouse or human donors that the phagocytosis of oxidized POS by RPE cells downregulates the synthesis of CFH in RPE [316].…”

Recent Advances on Imaging for Late-Stage Age-Related Macular Degeneration

“…Novel therapeutic techniques such as gene therapy using recombinant adeno-associated virus vectors delivering VEGF-inhibitory compounds and subsequent expression for long-term nAMD control are emerging [180,181] . However a staggering percentage of nAMD patients stabilized by anti-VEGF treatment still go onto to develop MA: more than 98 percent at 7 years in some studies [182] .New treatments for GA in dry AMD include complement pathway C3 and C5 inhbitors [183][184][185][186] .In all of these efforts, the ability to uitilize advances in imaging modalities to detect and document disease findings remains a critical stepping stone to future therapies.…”