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Exploring the choroidal vascular labyrinth and its molecular and structural roles in health and disease

Progress in Retinal and Eye Research, vol. 87, pp. 100994

Abstract

The choroid is a key player in maintaining ocular homeostasis and plays a role in a variety of chorioretinal diseases, many of which are poorly understood. Recent advances in the field of single-cell RNA sequencing have yielded valuable insights into the properties of choroidal endothelial cells (CECs). Here, we review the role of the choroid in various physiological and pathophysiological mechanisms, focusing on the role of CECs. We also discuss new insights regarding the phenotypic properties of CECs, CEC subpopulations, and the value of measuring transcriptomics in primary CEC cultures derived from post-mortem eyes. In addition, we discuss key phenotypic, structural, and functional differences that distinguish CECs from other endothelial cells such as retinal vascular endothelial cells. Understanding the specific clinical and molecular properties of the choroid will shed new light on the pathogenesis of the broad clinical range of chorioretinal diseases such as age-related macular degeneration, central serous chorioretinopathy and other diseases within the pachychoroid spectrum, uveitis, and diabetic choroidopathy. Although our knowledge is still relatively limited with respect to the clinical features and molecular pathways that underlie these chorioretinal diseases, we summarise new approaches and discuss future directions for gaining new insights into these sight-threatening diseases and highlight new therapeutic strategies such as pluripotent stem cell‒based technologies and gene therapy.

Authors 10

  1. Leiden University Medical Center

    Affiliation as printed

    Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands

  2. Leiden University Medical Center

    Affiliation as printed

    Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands

  3. Amsterdam University Medical Centers · University of Amsterdam

    Affiliation as printed

    Ocular Angiogenesis Group, Departments of Ophthalmology and Medical Biology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands

  4. Amsterdam UMC Location University of Amsterdam · Hôpital Ophtalmique Jules-Gonin · Fondation Asile des Aveugles · Amsterdam University Medical Centers · University of Amsterdam · University of Lausanne

    Affiliation as printed

    Ocular Angiogenesis Group, Departments of Ophthalmology and Medical Biology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands; Department of Ophthalmology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands; Department of Ophthalmology, University of Lausanne, Jules Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland

    Department of Ophthalmology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands

    Department of Ophthalmology, University of Lausanne, Jules Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland

    Ocular Angiogenesis Group, Departments of Ophthalmology and Medical Biology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands

  5. Leiden University Medical Center

    Affiliation as printed

    Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands

  6. Amsterdam University Medical Centers

    Affiliation as printed

    Department of Clinical Genetics, Section of Ophthalmogenetics, Amsterdam University Medical Centers, Amsterdam, the Netherlands

  7. Leiden University Medical Center

    Affiliation as printed

    Department of Vascular Surgery, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands

    Department of Vascular Surgery, Leiden University Medical Center, Leiden, the Netherlands

    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands

  8. Amsterdam University Medical Centers

    Affiliation as printed

    Department of Clinical Genetics, Section of Ophthalmogenetics, Amsterdam University Medical Centers, Amsterdam, the Netherlands

  9. Leiden University Medical Center

    Affiliation as printed

    Department of Medicine, Division of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, the Netherlands

  10. Leiden University Medical Center · Amsterdam University Medical Centers · University of Amsterdam

    Affiliation as printed

    Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands; Department of Ophthalmology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: camiel.boon@amsterdamumc.nl

    Department of Ophthalmology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands

    Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands

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References 496