Abstract
Abstract: :
Purpose: DBA/2J mice develop inherited glaucoma subsequent to anterior segment changes including pigment dispersion and iris stromal atrophy. We have investigated if the eyes of these mice exhibit markers of optic nerve injury and retinal stress described in human ocular diseases Methods: Eyes of 32–week old DBA/2J mice and healthy C57BL6 mice were analyzed by immunohistochemical means for the following antigens: Amyloid precursor protein (APP), activated caspase–3, glia fibrillary acid protein (GFAP), and alpha M integrin (CD11b). In addition, TUNEL staining was performed to identify apoptotic cells in the retina. Results: DBA/2J mice, in contrast to healthy C57BL6 mice, exhibited accumulation of APP immunoreactivity in the optic nerve head, although immunostaining was very faint in retinal ganglion cells of DBA/2J and C57BL6 mice. The retina of DBA/2J mice revealed strong staining of GFAP both in astrocytes and in the radial processes of Mueller glia cells, whereas in healthy C57BL6 mice GFAP staining was restricted to astrocytes. Interestingly, the retina of DBA/2J mice exhibited numerous CD11b positive cells, most likely activated microglia cells, which were not detected in healthy control mice. DBA/2J mice also demonstrated enhanced activated caspase–3 immunoreactivity in axonal processes of retinal ganglion cells, although TUNEL positive cells were not found. Conclusion: Accumulation of APP in the optic nerve head suggests that the axonal transport in these mice is severely compromised at the investigated stage of glaucoma development. Moreover, glia cell activation and immunostaining of activated caspase–3 in retinal ganglion cell processes indicates severe retinal stress, although apoptosis was not obvious. Further studies at earlier and later time points need to be performed in order to validate the analyzed antigens as appropriate markers of disease progression in this model of chronic glaucoma.
Keywords: gene/expression • microscopy: light/fluorescence/immunohistochemistry • pathology: experimental