Figure 4

Molecular interactions in the apical extracellular space of the pigmented (PE) and non-pigmented epithelium (NPE). Molecular network build in Ingenuity (http://www.Ingenuity.com), representing entries that are highly expressed and secreted in the apical extracellular space between NPE and PE. The top functions assigned to this network by Ingenuity were “Neurological disease, psychological disorders and cellular movement”. This network is contains many entries involved in matrix assembly and cytoskeleton organization (COL18A1, CTGF, DCN, FBN1, FBLN1, LTBP1, SPARC, and SPP1) and molecules involved in growth and proliferation (CTGF, EGF, IGF1, IGF2, IGFBP2-6, LTBP1, PTN, TGFB2 and VEGFA). IGF1 is a signature gene of the PE (yellow symbol). Together, these molecules are likely to be involved in the local turnover of the ECM between the PE-NPE layers of the CBE. We also identified several entries within the PE-NPE apical extracellular space of the CBE that are involved in amyloid-beta metabolism and plaque formation (A2M, APOE, CLU, SERPINA3, and TTR). Legend of different lines: Circles on top indicate direct relationships of entries with itself. Solid lines indicate that binding of the two proteins occur, arrows indicate that the first protein interfere with the expression or activity of the second protein.