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


CONCLUSIONS
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.
Georges
P
P
Save Sight Institute, GPO Box 4337, Sydney NSW 2001 Australia.
Cornish
E E
EE
Provis
J M
JM
Madigan
M C
MC
D000328:Adult; D027322:Amino Acid Transport System X-AG / Q000032:analysis* / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D005136:Eye Proteins / Q000032:analysis* / Q000276:immunology; D005865:Gestational Age; D005974:Glutamate-Ammonia Ligase / Q000032:analysis / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D009457:Neuroglia / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000276:immunology; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000276:immunology; D016708:Synaptophysin / Q000032:analysis / Q000276:immunology; D051020:bcl-X Protein / Q000032:analysis / Q000276:immunology
D027322:Amino Acid Transport System X-AG; D005136:Eye Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016708:Synaptophysin; D051020:bcl-X Protein; D005974:Glutamate-Ammonia Ligase