Reatividade da astroglia durante o desenvolvimento da retina de ratos submetidos a um modelo de hipóxia-isquemia pré-natal

Abstract

The hypoxic-ischemic insult (HI) is responsible for several CNS compromises during its development or at adulthood. Its consequences can cause varying degrees of retinopathy and visual impairment. Thus, investigating the effects of this insult on the retina may help to elucidate the mechanisms responsible for the consequences and thus outline therapeutical approaches. This work sought to mimic the most common human event, which occurs prenatally and may be irreversible. Using a model in which the uterine and ovarian flow of the pregnant rat is obstructed for 45 minutes on the 18th gestational day, a decrease in the optic nerve thickness and in the retinal projections in the dorsal lateral geniculate nucleus (NGLd), GCL loss and failure to maintain pupillary constriction have been reported. The aim of this study was to evaluate the retinal glial reactivity of Wistar rats during development (at two, nine, twenty three and thirteen postnatal days). The surgery for HI induction was performed with obstruction of uterine and ovarian flow (HI group) for 45 minutes on the eighteenth day of gestation. Animals that underwent all surgical procedure except for obstruction of blood flow constitute the sham-operated group (SH). Histological evaluation was performed to evaluate the development and response to the HI insult in cells of the retinal astroglial lineage, astrocytes and Muller's glia, using immunohistochemistry for glial fibrillary acidic protein (GFAP) and vimentin (VIM). Immunostaining for the GLAST glutamate transporter was also evaluated. The results showed that HI insult promotes an increase in GFAP and VIM labeling on the thirtieth postnatal day, as well as alters the immunostaining pattern for the GLAST transporter by anticipating the peak of labeling to the ninth day in the HI group. Taken together, the results show that, also in the retina, a gliosis occurs, as also described in other brain regions in rats submitted to this prenatal HI model. In addition to the results obtained for the GLAST transporter, we reinforce the hypothesis that glutamate transport alterations may contribute to glutamatergic excitotoxicity, one of the events responsible for neuronal death in this kind of lesion. Once more, we showed that the prenatal HI model used in this study is an important tool to be used in order to understand the mechanisms of the lesions caused by HI during development, as well as for the evaluation of possible therapeutic strategies.