Retinal pigment epithelial cells reduce vascular leak and proliferation in retinal neovessels.

Autor: Tzaridis S; The Lowy Medical Research Institute, La Jolla, CA, USA. stzaridis@scripps.edu.; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA. stzaridis@scripps.edu., Aguilar E; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA., Dorrell MI; The Lowy Medical Research Institute, La Jolla, CA, USA.; Point Loma Nazarene University, San Diego, CA, USA., Friedlander M; The Lowy Medical Research Institute, La Jolla, CA, USA.; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA., Eade KT; The Lowy Medical Research Institute, La Jolla, CA, USA.; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Jazyk: angličtina
Zdroj: Angiogenesis [Angiogenesis] 2024 Nov 27; Vol. 28 (1), pp. 1. Date of Electronic Publication: 2024 Nov 27.
DOI: 10.1007/s10456-024-09954-4
Abstrakt: In multiple neurodegenerative diseases, including age-related macular degeneration, retinitis pigmentosa, and macular telangiectasia type 2 (MacTel), retinal pigment epithelial (RPE)-cells proliferate and migrate into the neuroretina, forming intraretinal pigment plaques. Though these pigmentary changes are hallmarks of disease progression, it is unknown if their presence is protective or detrimental.Here, we first evaluated the impact of pigment plaques on vascular changes and disease progression in MacTel. In a retrospective, longitudinal study, we analyzed multimodal retinal images of patients with MacTel and showed that pigment plaques were associated with decreased vascular leakage and stabilized neovascular growth. We then modeled the underlying pathomechanisms of pigment plaque formation in aberrant neovascular growth using the very-low-density lipoprotein receptor mutant (Vldlr -/- ) mouse. Our data indicated that during RPE-proliferation, migration and accumulation along neovessels RPE-cells underwent epithelial-mesenchymal transition (EMT). Pharmacologic inhibition of EMT in Vldlr -/- mice decreased pigment coverage, and exacerbated neovascular growth and vascular leakage.Our findings indicate that the proliferation, migration and perivascular accumulation of RPE-cells stabilize vascular proliferation and exudation, thereby exerting a protective effect on the diseased retina. We conclude that interfering with this "natural repair mechanism" may have detrimental effects on the course of the disease and should thus be avoided.
Competing Interests: Declarations. Ethical approval: The studies were approved by the local ethics committees at each participating study site (Comité consultatif de protection des personnes dans la recherche biomédicale (CCPPRB); Human Research Ethics Committee (HREC); London City Road & Hampstead Research Ethics Committee; Sterling Institutional Review Board; Ethik-Kommission der Ärztekammer Westfalen-Lippe und der Medizinischen Fakultät der WWU Münster; The State of Israel Ministry of Health; The Chaim Sheba Medical Center; Ethik-Kommission - Medizinische Fakultät Bonn; University of Pennsylvania Institutional Review Board; Kantonale Ethikkommission Bern (KEK); University of Miami Human Subject Research Office), and were in adherence with the Declaration of Helsinki. All participants provided informed consent prior to participation. All animal experimental procedures were approved by The Scripps Research Institute Animal Care and Use Committee. Experiments were performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals (National Academies Press, 2011). Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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