INFLUENCE OF ApoE GENE ON NEURONAL AND GLIAL RETINAL CELLS

Abstract

Abstract: : Purpose:Study the influence of the ApoE gene on the number and morphology of retinal nuclear and ganglion cells. Methods:C57BL/6J (wild type–WT), ApoE deficient (knock out – KO) and transgenic mice recombinant for human ApoE 3 and 4 (TG 3 and TG4) were sacrificed at monthly age intervals and their retinal anatomy studied. At least two mice (four eyes) were sacrificed for each age and group. At random, one eye of each mouse was snap frozen, cryopreserved in OCT and processed for immunohistochemical analysis using specific antibodies directed against GFAP. The second eye was preserved in 4% PAF and processed for conventional histology. Systematic analysis of the staining and cell pattern was performed on the 3 to 5 transversal sections obtained through the optic nerve. Results:When comparing the wild type mice to KO ApoE mice and TG3 or TG4 mice up to 6–7 months old, no significant differences in the number or morpholgy of the nuclear and ganglion cells were detected. The pattern of GFAP positive staining of the retinal glial cells was also similar in all groups. When older mice were studied, the number of ganglion cells in retinas from wild type mice was, initially, strikingly higher than that observed in the ApoE KO mice. These differences reached statistical significance in some mice. These significant differences however were not observed in all mice of the same age group. Most studied mice from both groups of TG3 and TG4 showed normal cellular pattern. Absence of the ApoE gene in KO mice appear to affect the morphology and number of ganglion cells and the extent of GFAP positivity of the retinal glial cells. This affection was more obvious when some of the older mice were analyzed. These findings may indicate that the ApoE molecule is more crucial during aging, playing a role in preservation of the retinal anatomy. Reinsertion of recombinant human ApoE3 or ApoE4 genes to the KO mice corrects the above detected abnormalities. The fact that not all old KO and TG3 and TG4 showed the same exact pattern is puzzling. This may be associated with the possibility that some of the KO mice retained an undetected gene fraction encoding for ApoE. Conclusions:ApoE may play a role in the preservation of the retinal anatomy (and function?) especially during aging. The lack of constant and repeatable findings within the groups precludes any possible generalization at this stage.

Keywords: pathology: experimental • Muller cells • astrocytes: optic nerve head