Abstract
Age-related macular degeneration (AMD) is a neurodegenerative disease of the aging retina, in which patients experience severe vision loss. Therapies available to patients are limited and are only effective in a sub-population of patients. Future comprehensive clinical care depends on identifying new therapeutic targets and adopting a multi-therapeutic approach. With this goal in mind, this review examines the fundamental concepts underlying the development and progression of AMD and re-evaluates the pathogenic pathways associated with the disease, focusing on the impact of injury at the cellular level, with the understanding that critical assessment of the literature may help pave the way to identifying disease-relevant targets. During this process, we elaborate on responses of AMD vulnerable cells, including photoreceptors, retinal pigment epithelial cells, microglia, and choroidal endothelial cells, based on in vitro and in vivo studies, to select stressful agents, and discuss current therapeutic developments in the field, targeting different aspects of AMD pathobiology.
Highlights
Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in the Western hemisphere (Wong et al, 2014)
We will review the pathology and visual deficits associated with the different clinical subtypes of AMD and outline the pathogenic pathways linked to the development of AMD, with a focus on the growing body of evidence indicating that stress and injury to AMD vulnerable cells including photoreceptors, retinal pigment epithelial cells (RPE), retinal immune cells and choroidal endothelial cells, is a crucial component of the disease
It is important to note that geographic atrophy and choroidal neovascularization are not mutually exclusive as the atrophic retina may result in the development of a neovascular lesion, and wet AMD may proceed to macular atrophy
Summary
Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in the Western hemisphere (Wong et al, 2014). It is vital to further understand the molecular mechanisms underlying disease development and progression, in concert with the temporal development of pathological changes that occur in the retina. This is necessary in order to identify potential therapeutic targets. We will review the pathology and visual deficits associated with the different clinical subtypes of AMD and outline the pathogenic pathways linked to the development of AMD, with a focus on the growing body of evidence indicating that stress and injury to AMD vulnerable cells including photoreceptors, retinal pigment epithelial cells (RPE), retinal immune cells and choroidal endothelial cells, is a crucial component of the disease
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