Retinal regions shape human and murine Müller cell proteome profile and functionality. Issue 2 (5th November 2022)

• Record Type: Journal Article
• Authors: Kaplan, Lew; Drexler, Corinne; Pfaller, Anna M.; Brenna, Santra; Wunderlich, Kirsten A.; Dimitracopoulos, Andrea; Merl‐Pham, Juliane; Perez, Maria‐Theresa; Schlötzer‐Schrehardt, Ursula; Enzmann, Volker; Samardzija, Marijana; Puig, Berta; Fuchs, Peter; Franze, Kristian; Hauck, Stefanie M.; Grosche, Antje
• Is Part Of: Glia. Volume 71:Issue 2(2023)
• Page Start: 391
• Page End: 414
• Publication Date: 2022-11-05
• Subjects: retina -- macula -- Müller cells -- glial heterogeneity -- EPPK1; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.24283
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: The human macula is a highly specialized retinal region with pit‐like morphology and rich in cones. How Müller cells, the principal glial cell type in the retina, are adapted to this environment is still poorly understood. We compared proteomic data from cone‐ and rod‐rich retinae from human and mice and identified different expression profiles of cone‐ and rod‐associated Müller cells that converged on pathways representing extracellular matrix and cell adhesion. In particular, epiplakin (EPPK1), which is thought to play a role in intermediate filament organization, was highly expressed in macular Müller cells. Furthermore, EPPK1 knockout in a human Müller cell‐derived cell line led to a decrease in traction forces as well as to changes in cell size, shape, and filopodia characteristics. We here identified EPPK1 as a central molecular player in the region‐specific architecture of the human retina, which likely enables specific functions under the immense mechanical loads in vivo. Main Points: We defined Müller cells heterogeneity in the macular and peripheral human retina. Signaling pathways shaping this glial heterogeneity include proteins important for interaction with vesicular secretion, extracellular matrix and cell adhesion.