The expression of GABA_Areceptors during the development of the rabbit retina

Abstract

ABSTRACT.Purpose: Gamma-amino butyric acid (GABA) is a major inhibitory neurotransmitter in the retina, possibly participating in its normal development. The distribution of gamma-aminobutyric acid receptors was therefore examined in mature and developing rabbit retina by GABA A receptor alpha 1 and beta 2/3 subunit immunocytochemistry. Results: Beta 2/3 subunits appeared already at the E25 stage (25 days after gestation) although only weakly and irregularly. Alpha 1 subunit immunoreactivity was first observed at birth. On the fifth postnatal day, immunostaining was clearly seen in the inner plexiform layer, and weaker, in the outer plexiform layer. There were at this stage no well-delineated sublayers in either the inner or the outer plexiform layer, but three clearly defined sublayers appeared in the inner plexiform layer at PN10. Amacrine cell bodies now also appeared, labelling for both the GABA A receptor alpha 1 and the beta 2/3 chains. A punctuate labelling appeared in the outer plexiform layer. From the 20th postnatal day, the immunoreactivity was similar to that seen in adult rabbits. Conclusions: Like in the adult, the alpha 1 and beta 2/3 subunits of the GABA A receptor thus colocalize predominantly in certain amacrine cells and in processes of the inner plexiform layer during the development of the retina. The GABA A receptors appear later than GABA during the development of the rabbit retina, and functioning GABA neurotransmitter circuits appear to be assembled primarily after the 3rd to 5th postnatal day. Our results support the hypothesis that GABA may have other functions than mediating classic synaptic neurotransmission before the formation of receptors containing the alpha 1 and beta 2/3 subunits. Like in the brain, the alpha subunits may have more selective functions during the development than the beta subunits.

Developmental Expression of GABA_A Receptors in Retinal Transplants

“…Also, at this stage a punctuate immunoreactivity appeared in the outer plexiform layer. The immunoreactivity from PN 20 was comparable to that in the adult [35].…”

“…There seems to be an association between the time of development of GABA A receptors, and synaptogenesis and cellular differentiation [33]. The GABA A receptor · 1 and ß 2/3 subunits have been localized in the developing and the adult rabbit retinas [35,42,43]. In adult rabbit retina the GABA A receptor immunoreactivity is found in the inner and the outer plexiform layers, in certain subclasses of the amacrine cells and at low contents in certain bipolar and ganglion cells [37,[39][40][41][42]44].…”

“…The rabbits were sacrificed 4,6,11,14,18,21,25,35 and 111 days after the surgery; thus, the transplants attained the age equivalent (donor age + survival time after surgery) to E 19 (n = 2), 21 (n = 2), 26 (n = 2) and 29 (n = 2) and postnatal (PN) days 2 (n = 2), 5 (n = 2), 9 (n = 2), 19 (n = 2) and 95.…”

“…Therefore, the development of · 1 and ß 2/3 subunits of GABA A receptor, two common subunits of GABA A receptors, was studied in developing retinal transplants. Expression of these subunits during the development of the normal rabbit retina is known [35].…”

Expression of GABA transporter subtypes (GAT1, GAT3) in the developing rabbit retina

“…In our previous study, immunoreactivity of GABA A receptor a 1 and b 2/3 chains was first seen in the IPL of rabbit retina at PN0 and amacrine cell somata at PN5 (Hu et al 1998). The labeling pattern of both GABA A receptor chains (a 1 and b 2/3 ) was similar to that of adults at PN10, and their density reached the adult level at PN20 (Hu et al 1998). As seen in the present study, this development is quite similar to that of the appearance of GAT1 and GAT3 immunoreactivities demonstrated in this study.…”