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Müller cell expression of glutamate cycle related proteins and anti-apoptotic proteins in early human retinal development

¹ Save Sight Institute, University of Sydney, NSW 2006, Australia
² Research School of Biological Sciences, Australian National University, ACT 2605 Australia

Correspondence to:
Correspondence to:
Michele C Madigan
Save Sight Institute, GPO Box 4337, Sydney NSW 2001 Australia; michele{at}eye.usyd.edu.au

Aims: The distribution of glutamate cycle related proteins (glutamine synthetase (GS) and GLAST) and anti-apoptotic proteins (Bcl-2 and Bcl-X) was investigated in Müller cells during early human retinal development, relative to the onset of expression of synaptophysin, a presynaptic vesicle protein.

Methods: Using frozen sections of human fetal eyes (13–22 weeks gestation) (n = 10), Bcl-2, Bcl-X, GS, GLAST, and synaptophysin immunoreactivities (IR) were imaged using fluorescence microscopy and plotted as a function of eccentricity from the incipient fovea. Frozen sections of adult human retina (n = 4) were immunolabelled with antibodies to Bcl-2 and Bcl-X.

Results: Müller cell immunoreactivity for GS, GLAST, and Bcl-2 was initially detected in the incipient fovea, and then at more peripheral locations with increasing age. Synaptophysin-IR appeared earlier than all other target proteins. Within the synaptophysin-IR region, mature (differentiated) Müller cells expressed both Bcl-2 and Bcl-X-IR from 13 weeks gestation, ahead of GS-IR and GLAST-IR that were first seen at 14 weeks gestation. Additionally, from as early as 13 weeks gestation, ganglion cells and immature neuronal progenitor cells across the entire retina expressed Bcl-2-IR and Bcl-X-IR, respectively. In adult retina, ganglion cells and some bipolar cells expressed Bcl-X but not Bcl-2.

Conclusion: Müller cells express Bcl-2 and Bcl-X after synaptogenesis has commenced, but before the onset of GS and GLAST expression, suggesting a protective role for these proteins in Müller cells during the onset of glutamatergic transmission in early human retinal development.

Abbreviations: CRALBP, cellular retinaldehyde binding protein; EAAT1, excitatory amino acid transporter 1; GCL, ganglion cell layer; GLAST, L-glutamate-L-aspartate transporter; GS, glutamine synthetase; INL, inner nuclear layer; IPL, inner plexiform layer; IR, immunoreactivities; PBS, phosphate buffered saline

Keywords: cell survival; glutamine synthetase; l-glutamate-l-aspartate transporter; Bcl-2 family proteins; synaptogenesis

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