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

Abstract

In order to investigate the role of glia in relation to factors that affect the expression of beta-amyloid precursor protein ( βAPP) and B cell lymphoma oncogene protein (Bcl-2) in the central nervous tissue, the patterns of expression of βAPP and Bcl-2 in developing and mature rat retinas were studied immunocytochemically after intravitreal injection of alpha-aminoadipic acid ( α-AAA), a glutamate analogue and gliotoxin that is known to cause injury of retinal Müller glial cells. In normal developing retinas, βAPP 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 βAPP and Bcl-2 appeared in the endfeet and proximal part of the radial processes of Müller glial cells from the second postnatal week onwards. In rats that received intravitreal injection of α-AAA at birth, there was a loss of immunoreactivity to vimentin, and a delayed expressed on βAPP or Bcl-2 in Müller 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 Müller glial cells. In contrast, no detectable changes in the expression of βAPP and Bcl-2 were observed in retina that received α-AAA as adults. These results indicate that the gliotoxin α-AAA has long lasting effects on the expression of βAPP and Bcl-2 in Müller glial cells as well as neurons in the developing but not mature retinas. The loss of vimentin and delayed expression of βAPP and Bcl-2 in developing Müller glial cells suggests that the metabolic integrity of Müller cells was temporarily compromised, which may have adverse effects on developing neurons that are vulnerable or dependent on trophic support from the Müller glial cells.