Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor/retinal pigment epithelium/Bruch’s membrane/choriocapillaris complex

By I. Bhutto, G. Lutty. Molecular Aspects of Medicine, 2012

980 citations recorded by the source corpus.

There is a mutualistic symbiotic relationship between the components of the photoreceptor/retinal pigment epithelium (RPE)/Bruch’s membrane (BrMb)/choriocapillaris (CC) complex that is lost in AMD. Which component in the photoreceptor/RPE/BrMb/CC complex is affected first appears to depend on the type of AMD. In atrophic AMD (~85–90% of cases), it appears that large confluent drusen formation and hyperpigmentation (presumably dysfunction in RPE) are the initial insult and the resorption of these drusen and loss of RPE (hypopigmentation) can be predictive for progression of geographic atrophy (GA). The death and dysfunction of photoreceptors and CC appear to be secondary events to loss in RPE. In neovascular AMD (~10–15% of cases), the loss of choroidal vasculature may be the initial insult to the complex. Loss of CC with an intact RPE monolayer in wet AMD has been observed. This may be due to reduction in blood supply because of large vessel stenosis. Furthermore, the environment of the CC, basement membrane and intercapillary septa, is a proinflammatory milieu with accumulation of complement components as well as proinflammatory molecules like CRP during AMD. In this toxic milieu, CC die or become dysfunction making adjacent RPE hypoxic. These hypoxic cells then produce angiogenic substances like VEGF that stimulate growth of new vessels from CC, resulting in choroidal neovascularization (CNV). The loss of CC might also 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 within 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.

Subfields: Ophthalmology, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/4607db6bcffbcef27e6d02e3291d8bfc93be0989

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Ophthalmology

In Radiology, Nuclear Medicine and Imaging

Citations in the corpus

Optical coherence tomography angiography (2017, background): “It has been postulated that the hypoxic environment created by the choriocapillaris loss may induce release of VEGF by the intact overlying retinal pigment epithelial cells, which may, in turn, give rise to the MNV (Bhutto and Lutty, 2012).”
The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age-Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults (2016, background): “The retinal blood flow is disturbed in both dry and CNV/AMD type [208]; the reduction in choroidal perfusion has been positively correlated with the disease progression [205].”
Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye (2015, background): “Whether the RPE or choriocapillaris alterations are the primary event in pathogenesis has been a matter of debate (26).”