Drusen Formation Linked to Extracellular Vesicle Release by RPE Cells, as Potential Biomarker of AMD

Article: First Evidence Linking Extracellular Vesicles with Drusen Formation and Age-Related Macular Degeneration
Source: University of Colorado Medicine
Published: November 12, 2021

Size distribution of EVs in control (green) and CSE (red) ipRPE cells;
in CSE ipRPE cells, EVs exhibited directional release via the apical surface

Drusen are deposits that accumulate under the retina, between the retinal pigmented epithelium (RPE) and Bruch's membrane of the underlying choriocapillaris (of the choroid). The accumulation of drusen signals the, often age-related, decline in RPE function in recycling and maintaining photoreceptor health, leading to retinal diseases such as age-related macular degeneration (AMD). Researchers have for the first time observed evidence of RPE cells releasing exosomes that contain both normal proteins and proteins that are associated with drusen. This occurs in normal physiological conditions, and is increased 20 times under conditions of cellular stress. Moreover, the secretion of extracellular vesicles (EVs) by the RPE cells exhibited polarity or directionality. The authors write, "Notably, drusen-associated proteins exhibited distinctive directional secretion modes in homeostatic conditions and, differential modulation of this directional secretion in response to AMD stressors." For example, when treated with cigarette smoke extract (CSE) as a stressor and known risk factor for AMD, the RPE cells exhibited notably increased release of EVs from their apical surface compared to their basal surface. The RPE and Bruch's membrane share an apex-to-apex attachment, due to involution of the optic cup during development. The researchers suggest that these drusen-associated proteins could provide an early biomarker of AMD. First author of the study remarks, "Knowing that extracellular vesicles are releasing drusen-associated proteins presents an opportunity for novel diagnostic and therapeutical approaches. If we can define assays to measure these proteins released in these exosomes, we could potentially diagnose the disease early." Senior researcher of the project adds, "If we understand how drusen form and what cells or mechanisms contribute to their formation, we may be able to control the formation of drusen and slow down or even, perhaps prevent, some of the pathological events leading to AMD." They conclude, "Collectively, our results strongly support an active role of RPE-derived EVs as a key source of drusen proteins and important contributors to drusen development and growth."

My rating of this study: ⭐⭐⭐

Flores-Bellver M, Mighty J, Aparicio-Domingo S, et al. "Extracellular vesicles released by human retinal pigment epithelium mediate increased polarised secretion of drusen proteins in response to AMD stressors." Journal of Extracellular Vesicles.  10(13):e12165. 8 November 2021. https://doi.org/10.1002/jev2.12165