Expression of β-amyloid precursor and Bcl-2 proto-oncogene proteins in rat retinas after intravitreal injection of aminoadipic acid

In order to investigate the role of glia in relation to factors that affect the expression of beta-amyloid precursor protein (beta APP) and B cell lymphoma oncogene protein (Bcl-2) in the central nervous tissue, the patterns of expression of beta APP and Bcl-2 in developing and mature rat retinas were studied immunocytochemically after intravitreal injection of alpha-aminoadipic acid (alpha-AAA), a glutamate analogue and gliotoxin that is known to cause injury of retinal Muller glial cells. In normal developing retinas, beta APP and Bcl-2 were expressed primarily but transiently in a small number of neurons in the ganglion cell layer during the first postnatal week. Immunoreactivity of beta APP and Bcl-2 appeared in the endfeet and proximal part of the radial processes of Muller glial cells from the second postnatal week onwards. In rats that received intravitreal injection of alpha-AAA at birth, there was a loss of immunoreactivity to vimentin, and a delayed expressed on beta APP or Bcl-2 in Muller glial cells until 3-5 weeks post-injection. Immunoreactive neurons were also observed in the inner retina especially in the ganglion cell layer from 5 to 35 days after injection. A significant reduction in numerical density of cells with large somata in the ganglion cell layer was observed in the neonatally injected retinas at P56, which was accompanied by an increased immunostaining in radial processes of Muller glial cells. In contrast, no delectable changes in the expression of beta APP and Bcl-2 were observed in retina that received alpha-AAA as adults. These results indicate that the gliotoxin alpha-AAA has long lasting effects on the expression of beta APP and Bcl-2 in Muller glial cells as well as neurons in the developing but not mature retinas. The loss of vimentin and delayed expression of beta APP and Bcl-2 in developing Muller glial cells suggests that the metabolic integrity of Muller cells was temporarily compromised, which may have adverse effects on developing neurons that are vulnerable or dependent on trophic support from the Muller glial cells. (C) 1999 Elsevier Science Ltd. All rights reserved.