Neuroprotection for Age-Related Macular Degeneration

Jonathan B Lin; Yusuke Murakami; Joan W Miller; Demetrios G Vavvas

doi:10.1016/j.xops.2022.100192

Neuroprotection for Age-Related Macular Degeneration

Ophthalmol Sci. 2022 Jul 5;2(4):100192. doi: 10.1016/j.xops.2022.100192. eCollection 2022 Dec.

Authors

Jonathan B Lin¹, Yusuke Murakami^{1

2}, Joan W Miller¹, Demetrios G Vavvas¹

Affiliations

¹ Ines and Frederick Yeatts Retina Research Laboratory, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts.
² Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Abstract

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.

Keywords: AD, Alzheimer disease; ALA, alpha lipoic acid; AMD, age-related macular degeneration; AREDS, Age-Related Eye Disease Study; AREDS2, Age-Related Eye Disease Study 2; Age-related macular degeneration; CFH, complement factor H; CNTF, ciliary neurotrophic factor; GA, geographic atrophy; HTRA1, high-temperature requirement A1; IOP, intraocular pressure; Neuroprotection; RBP, retinol-binding protein; RGC, retinal ganglion cell; RIPK3, receptor-interacting serine/threonine-protein kinase 3; ROS, reactive oxygen species; RPE, retinal pigment epithelium; Retinal degeneration; VA, visual acuity; iPSC, induced pluripotent stem cell.

Publication types

Review