Neuroprotection for Age-Related Macular Degeneration

• Published in: Ophthalmology science (Online) Vol. 2; no. 4; p. 100192
• Main Authors: Lin, Jonathan B., Murakami, Yusuke, Miller, Joan W., Vavvas, Demetrios G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-12-2022; Elsevier
• Subjects: Age-related macular degeneration; Neuroprotection; Retinal degeneration; Translational Science Reviews; Neuroprotection; AREDS2; RBP; CNTF; AD; CFH; RIPK3; RPE; iPSC; HTRA1; IOP; VA; RGC; Age-related macular degeneration; ALA; ROS; Retinal degeneration; AMD; AREDS; GA; AREDS, Age-Related Eye Disease Study; AREDS2, Age-Related Eye Disease Study 2; RGC, retinal ganglion cell; VA, visual acuity; GA, geographic atrophy; IOP, intraocular pressure; RPE, retinal pigment epithelium; AMD, age-related macular degeneration; CFH, complement factor H; RBP, retinol-binding protein; HTRA1, high-temperature requirement A1; ALA, alpha lipoic acid; AD, Alzheimer disease; CNTF, ciliary neurotrophic factor; ROS, reactive oxygen species; RIPK3, receptor-interacting serine/threonine-protein kinase 3; iPSC, induced pluripotent stem cell
• ISSN: 2666-9145; 2666-9145
• DOI: 10.1016/j.xops.2022.100192

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Early to intermediate AMD is characterized by the accumulation of lipid- and protein-rich drusen. Late stages of the disease are characterized by the development of choroidal neovascularization, termed “exudative” or “neovascular AMD,” or retinal pigment epithelium (RPE) cell and photoreceptor death, termed “geographic atrophy” (GA) in advanced nonexudative AMD. Although we have effective treatments for exudative AMD in the form of anti-VEGF agents, they have no role for patients with GA. Neuroprotection strategies have emerged as a possible way to slow photoreceptor degeneration and vision loss in patients with GA. These approaches include reduction of oxidative stress, modulation of the visual cycle, reduction of toxic molecules, inhibition of pathologic protein activity, prevention of cellular apoptosis or programmed necrosis (necroptosis), inhibition of inflammation, direct activation of neurotrophic factors, delivery of umbilical tissue–derived cells, and RPE replacement. Despite active investigation in this area and significant promise based on preclinical studies, many clinical studies have not yielded successful results. We discuss selected past and current neuroprotection trials for AMD, highlight the lessons learned from these past studies, and discuss our perspective regarding remaining questions that must be answered before neuroprotection can be successfully applied in the field of AMD research.