Abstract
Purpose: :
The neuronal changes in a mouse model of inherited glaucoma (DBA/2J) were assessed to address the following questions: 1. Which cell populations are affected? 2. Are there types of resistant ganglion cells? 3. Is there evidence for impaired axonal transport?
Methods: :
The majority of DBA/2J mice have developed severe glaucoma in one or both eyes by the age of 1 year. The severity of ganglion cell degeneration was assessed by optic nerve staining. Retinas from severely affected eyes, from unaffected eyes that had escaped the disease, and from 3–mo–old (pre–disease) DBA/2J mice were stained with antibodies to a variety of markers for ganglion–, amacrine–, horizontal–, and bipolar cells and imaged by high–resolution confocal microscopy. In addition, the morphology of 154 individual ganglion cells from affected and normal retinas was visualized using particle–mediated dye transfer or retrograde labeling with rhodamine–dextran followed by reverse photodynamics.
Results: :
We found no evidence of damage to any other cell type than ganglion cells at that age. Three different amacrine cell populations (cholinergic starburst amacrine cells, dopaminergic amacrine cells and AII amacrine cells) displayed no abnormalities in morphology or absolute numbers. Likewise, no evidence for horizontal cell damage or loss of rod bipolar cells was detected. In contrast, ganglion cells were found to be severely depleted. Visualization of surviving individual ganglion cells revealed no preponderance of any particular ganglion cell type. Abnormal cells with thin axons, shrunken somata, and remodeled dendrites were commonly observed. Interestingly, the loss of ganglion cells was not uniform over the whole retina. Rather, even in severely affected eyes, regions of surviving cells persisted, radiating from the optic nerve head in fan–shaped sectors. These regions contained ganglion cells that were normal in appearance.
Conclusions: :
Our data is compatible with damage to axon bundles at the optic nerve head as an early lesion. As a lamina cribrosa seems to be absent in mice, optic nerve glia could play a role in the ganglion cell pathology observed in DBA/2J mice.
Keywords: ganglion cells • imaging/image analysis: non-clinical • cell survival