TY - CHAP
T1 - Bruch’s Membrane and the Choroid in Age-Related Macular Degeneration
AU - Edwards, Malia
AU - Lutty, Gerard A.
N1 - Funding Information:
Acknowledgments Studies from the Lutty lab were funded by NIH grants EY016151 (GL), EY09357 (GL), EY01765 (Wilmer); the Altsheler-Durell Foundation; American Health Assistance Foundation (Bright Focus); and an unrestricted gift from Research to Prevent Blindness (RPB) (Wilmer). Gerard Lutty is an RPB Senior Investigator. The authors acknowledge D. Scott McLeod for creation of the Figures and Imran Bhutto, Rhonda Grebe, Takuya Hasegawa, Scott McLeod, Carol Merges, Masa Nakanishi, Johanna Seddon, Makoto Taomoto, and Koichi Uno for their contribution to the studies from the Lutty lab.
Publisher Copyright:
© 2021, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Age-related macular degeneration
KW - Bruchs membrane
KW - Choriocapillaris
KW - Choroid
KW - Choroidal neovascularization
KW - Geographic atrophy
KW - Inflammation
UR - http://www.scopus.com/inward/record.url?scp=85104353942&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85104353942&partnerID=8YFLogxK
U2 - 10.1007/978-3-030-66014-7_4
DO - 10.1007/978-3-030-66014-7_4
M3 - Chapter
C2 - 33847999
AN - SCOPUS:85104353942
T3 - Advances in Experimental Medicine and Biology
SP - 89
EP - 119
BT - Advances in Experimental Medicine and Biology
PB - Springer
ER -