Bruch's Membrane and the Choroid in Age-Related Macular Degeneration.

Malia Edwards, Gerard A Lutty

Advances in experimental medicine and biology 2021

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A healthy choroidal vasculature is necessary to support the retinal pigment epithelium (RPE) and photoreceptors, because there is a mutualistic symbiotic relationship between the components of the photoreceptor/retinal pigment epithelium (RPE)/Bruch's membrane (BrMb)/choriocapillaris (CC) complex. This relationship is compromised in age-related macular degeneration (AMD) by the dysfunction or death of the choroidal vasculature. This chapter will provide a basic description of the human Bruch's membrane and choroidal anatomy and physiology and how they change in AMD.The choriocapillaris is the lobular, fenestrated capillary system of choroid. It lies immediately posterior to the pentalaminar Bruch's membrane (BrMb). The blood supply for this system is the intermediate blood vessels of Sattler's layer and the large blood vessels in Haller's layer.In geographic atrophy (GA), an advanced form of dry AMD, large confluent drusen form on BrMb, and hyperpigmentation (presumably dysfunction in RPE) appears to be the initial insult. The resorption of these drusen and loss of RPE (hypopigmentation) can be predictive for progression of GA. The death and dysfunction of CC and photoreceptors appear to be secondary events to loss in RPE. The loss of choroidal vasculature may be the initial insult in neovascular AMD (nAMD). We have observed a loss of CC with an intact RPE monolayer in nAMD, by making RPE hypoxic. These hypoxic cells then produce angiogenic substances like vascular endothelial growth factor (VEGF), which stimulate growth of new vessels from CC, resulting in choroidal neovascularization (CNV). Reduction in blood supply to the CC, often stenosis of intermediate and large blood vessels, is associated with CC loss.The polymorphisms in the complement system components are associated with AMD. In addition, the environment of the CC, basement membrane and intercapillary septa, is a proinflammatory milieu with accumulation of proinflammatory molecules like CRP and complement components during AMD. In this toxic milieu, CC die or become dysfunctional even early in AMD. The loss of CC might be a stimulus for drusen formation since the disposal system for retinal debris and exocytosed material from RPE would be limited. Ultimately, the photoreceptors die of lack of nutrients, leakage of serum components from the neovascularization, and scar formation.Therefore, the mutualistic symbiotic relationship of the photoreceptor/RPE/BrMb/CC complex is lost in both forms of AMD. Loss of this functionally integrated relationship results in death and dysfunction of all of the components in the complex.

Citation

Malia Edwards, Gerard A Lutty. Bruch's Membrane and the Choroid in Age-Related Macular Degeneration. Advances in experimental medicine and biology. 2021;1256:89-119