Abstract
BackgroundThe neuroepithelia of the choroid plexus (CP) in the brain and the ciliary body (CB) of the eye have common embryological origins and share similar micro-structure and functions. The CP epithelium (CPE) and the non-pigmented epithelium (NPE) of the CB produce the cerebrospinal fluid (CSF) and the aqueous humor (AH) respectively. Production and outflow of the CSF determine the intracranial pressure (ICP); production and outflow of the AH determine the intraocular pressure (IOP). Together, the IOP and ICP determine the translaminar pressure on the optic disc which may be involved in the pathophysiology of primary open angle glaucoma (POAG). The aim of this study was to compare the molecular machinery of the secretory neuroepithelia of the CP and CB (CPE versus NPE) and to determine their potential role in POAG.MethodsWe compared the transcriptomes and functional annotations of healthy human CPE and NPE. Microarray and bioinformatic studies were performed using an Agilent platform and the Ingenuity Knowledge Database (IPA).ResultsBased on gene expression profiles, we found many similar functions for the CPE and NPE including molecular transport, neurological disease processes, and immunological functions. With commonly-used selection criteria (fold-change > 2.5, p-value < 0.05), 14% of the genes were expressed significantly differently between CPE and NPE. When we used stricter selection criteria (fold-change > 5, p-value < 0.001), still 4.5% of the genes were expressed differently, which yielded specific functions for the CPE (ciliary movement and angiogenesis/hematopoiesis) and for the NPE (neurodevelopmental properties). Apart from a few exceptions (e.g. SLC12A2, SLC4A4, SLC4A10, KCNA5, and SCN4B), all ion transport protein coding genes involved in CSF and AH production had similar expression profiles in CPE and NPE. Three POAG disease genes were expressed significantly higher in the CPE than the NPE, namely CDH1, CDKN2B and SIX1.ConclusionsThe transcriptomes of the CPE and NPE were less similar than we previously anticipated. High expression of CSF/AH production genes and candidate POAG disease genes in the CPE and NPE suggest that both might be involved in POAG.
Highlights
The neuroepithelia of the choroid plexus (CP) in the brain and the ciliary body (CB) of the eye have common embryological origins and share similar micro-structure and functions
The aims of this study were (1) to compare the gene expression profiles and functional annotation of the choroid plexus epithelium (CPE) and non-pigmented epithelium (NPE) in order to determine common properties and potential specific functions and (2) to determine CPE/NPE highly and expressed genes coding for ion transport proteins involved in cerebrospinal fluid (CSF)/aqueous humor (AH) production and (3) for genes previously associated with primary open angle glaucoma (POAG)
For the K+ channel, we only presented the highly and/or statistical significant different expressed genes of the CPE and NPE; Column 2 - Present in: The presence of the different ion channels and ion transporters are reviewed in [30] for the CPE and [20] for the NPE; Column 3 - Coding genes: the genes coding for the ion channels and ion transporters listed in column 1; Column 4 - High gene expr.: Here we indicate the genes that are highly expressed in the CPE and/or NPE according to our gene expression microarray data of the CPE and NPE
Summary
The neuroepithelia of the choroid plexus (CP) in the brain and the ciliary body (CB) of the eye have common embryological origins and share similar micro-structure and functions. In specialized areas of the central nervous system (CNS), these cells retain their epithelial nature and differentiate into fluid-secreting cells: the neuroepithelia of the ocular ciliary body and the choroid plexus epithelium of the brain [4,5,6,7,8,9]. These tight single-cell layers function together with the outer blood-retina barrier and the blood–brain barrier to maintain CNS homeostasis and are implicated in diseases like age-related macular degeneration, primary open-angle glaucoma (POAG) and Alzheimer’s disease. We determined the RNA expression profiles and predicted functional properties of five adult human neuroepithelia using a single microarray and bioinformatics platform: the central and peripheral retinal pigment epithelium [13,14,15], the pigmented and nonpigmented neural epithelia of the ocular ciliary body (CB) [16], and the choroid plexus neural epithelium (CPE) of the brain [17]
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