Disrupted polarized secretion of retinal pigment epithelium may help drive pathology.
Evidence
This review synthesizes mechanistic evidence on RPE-sEV trafficking, apical and basolateral cargo profiles, and stress-induced disruption under oxidative and hypoxic conditions relevant to AMD.
Caveat
The therapeutic proposal to repair RPE intracellular trafficking is mechanistic and conceptual, not evidence from clinical outcome testing in the abstract.
Simplified
The pathogenesis of (AMD) is intrinsically driven by retinal pigment epithelium (RPE) dysfunction. Under physiological conditions, the strictly polarized secretion of (sEVs) by the RPE dictates outer retinal homeostasis. In response to oxidative and hypoxic stress, this secretory architecture is profoundly disrupted, transforming sEVs into mediators of drusen formation, inflammation, and neovascularization. This review systematically delineates the molecular machinery governing RPE-sEV trafficking, unveiling the distinct protein and miRNA cargo profiles segregated between the apical and basolateral domains. We highlight the unique secretory features of RPE and elucidate how AMD stressors disrupt this polarity via cytoskeletal collapse, secretory autophagy, and Rab GTPase dysregulation. Consequently, this altered sEV secretion abolishes apical neurotrophic support while deteriorating the basolateral microenvironment. Crucially, this establishes a vicious pathological loop where microenvironmental deterioration and sEV dysregulation are mutually causative. Recognizing dysregulated sEV polarity as a contributing factor to AMD, we propose that repairing RPE intracellular trafficking offers a fundamental strategy to restore secretory homeostasis and impede disease progression.
Full Text
We can’t show the full text here under this license.
3 authors received research support from National High Level Hospital Clinical Research Funding, including funding for Ruiyi Yan's research under grant 2025-PUMCH-C-027.
