Desmosome and Hemidesmosome Disassembly in Retinal Pigmented Epithelium: Intersection with the Exosome Pathway.

The retinal pigmented epithelium (RPE) forms the outer blood-retinal barrier, and like other epithelia it has several different types of cell-cell junctions, such as desmosomes. The RPE provides key metabolic and nutrient support to photoreceptors and the function of normal vision. The RPE is a principal location of disease-associated changes in age-related macular degeneration (AMD), due to its essential role in visual homeostasis. There are no robust early indicators of AMD or disease progression, a need that could be filled by the development of early AMD biomarkers. Exosomes are lipid bilayer membrane vesicles of nanometer sizes that are released via a dedicated machinery by all cells and carry out a multitude of functions related to cellular signaling and waste management. In the RPE, they are released from both the apical and basal sides, and the cargo composition reflects this polarization. We have recently shown that exosomes released from the basolateral side of RPE cells under chronic oxidative stress conditions contain desmosome and hemidesmosome proteins. Here we discuss the composition of desmosomes and hemidesmosomes in the RPE, and the potential of these exosome-associated components as biomarkers of early RPE dysfunction preceding AMD symptoms detectable in the current clinical setting. How cargo loading into basolateral exosomes is controlled in polarized epithelia such as RPE, is also discussed.