Adult human retinal Müller glia display distinct peripheral and macular expression of CD117 and CD44 stem cell-associated proteins

Abstract

Experimental evidence suggests human Müller glia exhibit neural progenitor properties in vitro. CD117 and CD44 are known to be expressed by stem cells, the survival of which appears to depend critically on interactions with hyaluronan-rich extracellular matrix (ECM). Here, we characterise Müller glia expression of CD117 and CD44 in normal adult human retina and describe how it correlates with hyaluronan distribution in ocular ECM. By using chromogen-based immunohistochemistry, CD117 expression was found in entire Müller glia cytoplasm spanning from inner to outer limiting membrane in both peripheral retina (PR) and macular retina (MR), mirroring expression of the established Müller glia marker vimentin. Unlike vimentin, CD117 was also strongly expressed by Müller glia nuclei. Relative to total inner nuclear layer (INL) nuclei, more CD117+ Müller glia nuclei were seen in PR than MR. By contrast, CD44 expression was found predominantly in Müller glia apical processes of PR; no expression was found in MR. Astral blue staining demonstrated the presence of hyaluronan in cortical vitreous and the interphotoreceptor matrix (IPM) in both MR and PR. Our findings demonstrate that: (i) both CD117 and CD44 are expressed by human adult Müller glia; (ii) CD117 is a robust nuclear and cytoplasmic immunohistochemical marker of Müller glia; and (iii) that while CD117 is expressed by the entire Müller glia in both PR and MR, CD44 is only expressed by Müller glia apices in PR. Since the apices of Müller glia are in direct contact with the hyaluronan-rich IPM, the Müller glia-IPM interface in PR is likely a favourable region for supporting progenitor or stem cell-like signalling. These observations provide novel insights into potential stem-cell favouring microenvironments in mature human retina.