Expression of beta-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 lym phoma 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 we re studied immunocytochemically after intravitreal injection of alpha-amino adipic acid (alpha-AAA), a glutamate analogue and gliotoxin that is known t o cause injury of retinal Muller glial cells. In normal developing retinas, beta APP and Bcl-2 were expressed primarily but transiently in a small num ber 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 postnat al week onwards. In rats that received intravitreal injection of alpha-AAA at birth, there was a loss of immunoreactivity to vimentin, and a delayed e xpressed on beta APP or Bcl-2 in Muller glial cells until 3-5 weeks post-in jection. Immunoreactive neurons were also observed in the inner retina espe cially in the ganglion cell layer from 5 to 35 days after injection. A sign ificant reduction in numerical density of cells with large somata in the ga nglion cell layer was observed in the neonatally injected retinas at P56, w hich 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 adul ts. These results indicate that the gliotoxin alpha-AAA has long lasting ef fects 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 cel ls suggests that the metabolic integrity of Muller cells was temporarily co mpromised, which may have adverse effects on developing neurons that are vu lnerable or dependent on trophic support from the Muller glial cells. (C) 1 999 Elsevier Science Ltd. All rights reserved.