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

Abstract

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. 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. 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. 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.