Developmental Expression of GABA _A Receptors in Retinal Transplants

Abstract

γ-Aminobutyric acid (GABA) has transiently been found in certain retinal cells during development, and thus it has been suggested that besides its role as an inhibitory neurotransmitter, it also plays a role during the development of the retina. Further it has been suggested that this developmental role of GABA is mediated through GABA_A receptors. Retinal cell transplants are being tried for the treatment of degenerative retinal disorders. Even though the donor tissue continues to proliferate, to develop and to differentiate after transplantation, its development is not entirely normal. Various neurotransmitters have been found in retinal transplants, but the receptors, which are needed for their action, have not been demonstrated. It was therefore of interest to see the expression of GABA_A receptors during the development of the transplants. Embryonic day (E) 15 rabbit retinas were transplanted into the eyes of adult rabbits. Transplants were allowed to survive for various times so that the grafts attained the equivalent ages of (donor age + survival time) E 19, 21, 26, 29 and postnatal (PN) day 2, 5, 9, 19 and 95. On formaldehyde-fixed cryostat sections of the transplant tissue immunohistochemistry was performed. Antibodies against the α₁ and β_2/3 subunits of the GABA_A receptors were used to demonstrate these receptors. No immunoreactivity was detected in transplants of ages E 19 and 22. The GABA_A receptor β_2/3 subunit first appeared in E 29 transplants, whereas the GABA_A receptor α₁ subunit was first detected at PN 2. At these ages faint immunoreactivity was detected in certain plexiform layers in the transplants. In older ages the immunoreactivity increased and also appeared in certain cells lying in between the rosettes along with the plexiform layers that are equivalent to the inner and the outer plexiform layers of the normal retina. The development of the GABA_A receptor α₁ and β_2/3 subunit immunoreactivity compared well with that during the development of the normal retina. The results suggest that GABA present in the retinal transplants can exert its action through its receptors.