Abstract
Purpose: :
In glaucoma, active transport between the retina and brain diminishes as a function of age and ocular pressure elevation. This loss occurs in a retinotopically constrained fashion evident in the superior colliculus (SC). In response to deprivation, target sites often react with mechanisms to restore lost inputs and/or to preserve existing connections. We compared the pattern of transport loss with the localization of brain-derived neurotrophic factor (BDNF) and the astrocyte marker glial fibrillary acidic protein (GFAP) in the SC.
Methods: :
We used two rodent models: the DBA/2J mouse model of hereditary glaucoma and a more acute model of high pressure glaucoma - the microbead occlusion model (MOM). DBA/2J mice between 5 and 12 months of age were used. For the MOM model, we elevated IOP by injecting inert polystyrene beads into the anterior chamber in C57 mice and Brown Norway rats. We assessed active anterograde transport by intravitreal injection of cholera toxin beta subunit. Brains were harvested, sectioned and immunostained to visualize the relationship between transport loss and expression of BDNF and GFAP.
Results: :
BDNF and GFAP were increased in colliculi exhibiting transport loss. This increase occurred in a specific pattern within the superficial (retinorecipient) SC - BDNF and GFAP elevations were restricted to the site of transport loss while areas of normal transport displayed low levels of both. In the layers of the deep SC adjacent to the retinorecipient SC, elevations of BDNF and GFAP were widespread, subtending a much larger area of the SC than the transport deficits. BDNF and GFAP colocalized to a large degree within both regions of the SC.
Conclusions: :
The elevation in BDNF and GFAP at the site of transport loss may be an attempt to restore or preserve function. Colocalization of BDNF and GFAP indicate that BDNF increases are due to astrocytic activity. That these increases also occur in the deep SC suggest that BDNF-expressing astrocytes are migrating to the site of transport loss from non-retinorecipient areas. Furthermore, that BDNF and GFAP elevation occur only in the region of transport deficit in the superficial SC suggests that loss of transport is the major factor initiating this response.
Keywords: superior colliculus/optic tectum • growth factors/growth factor receptors • astrocyte