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Müller cell expression of glutamate cycle related proteins and anti-apoptotic proteins in early human retinal development
  1. P Georges1,
  2. E E Cornish1,
  3. J M Provis1,2,
  4. M C Madigan1
  1. 1Save Sight Institute, University of Sydney, NSW 2006, Australia
  2. 2Research School of Biological Sciences, Australian National University, ACT 2605 Australia
  1. Correspondence to: Michele C Madigan Save Sight Institute, GPO Box 4337, Sydney NSW 2001 Australia; michele{at}eye.usyd.edu.au

Abstract

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.

  • 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
  • cell survival
  • glutamine synthetase
  • l-glutamate-l-aspartate transporter
  • Bcl-2 family proteins
  • synaptogenesis

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