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Michael Scholz, Friedrich Paulsen, Helmut Brandstätter, Hanna Regus-Leidig, Jenny Atorf, Jan Kremers; Neurodegenerative Changes In The Retina Of The Dba/2j Mouse. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2452.
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The DBA2/J mouse is commonly used as a model of secondary angle-closure glaucoma accompanied by an age-dependent increase of IOP. Nevertheless recent studies revealed that neurodegenerative processes in those animals individually occur without a stringent correlation to elevated IOP. The aim of our studies was (i) to describe and characterize the neurodegenerative changes and the neuronal function of the DBA2/J retina and (ii) to find factors, in addition to elevated IOP, which could also be involved in the onset or the progression of neurodegenerative changes in the DBA2/J eye.
We performed scotopic flash-ERG and light-adapted flicker-ERG measurements in DBA/2J, DBA/2J-Rj and C57/Bl6 mice at different ages. In-situ Hybridization and immunhistochemical staining on sagittal eye sections and/or retina whole-mount preparations in D2J and control strains were performed. Aqueous humor analyses with a Mouse Cytokine Antibody-Array of 10 month old D2J eyes with and without optic nerve neuropathy were done. Histomorphological and ultrastructural analysis on retinal sections were performed to determine morphological differences in the inner neuronal layers of the DBA/2J retina.
DBA/2J mice showed lower flicker ERG responses than C57/Bl6 mice already at younger ages. In both strains the ERG responses decrease as a function of age, but with a stronger decrease in the DBA/2J mice. Immunhistochemical α-PAG staining showed a partial loss of staining of the outer segments of the cone photoreceptors in 36% of the investigated D2J retinas (n=14) at 10 months of age. Detailed analysis of ERG data revealed significant differences in the neuronal responses of the INL of the retina between DBA/2J mice with and without α-PAG staining loss. Ultrastructural analyses revealed morphological detectable differences in number and shape of functional ribbon synapses in DBA/2J and C57/Bl6 retinas. Antibody-Array Analysis showed Osteopontin (OPN) as an age-dependently increased AH factor associated with optic nerve degenerations in DBA/2J mice.
The results on the origin and the characteristics of neurodgenerative changes within the aging DBA/2J eyes indicate complex changes of retinal neurons and synapses in those animals. The presented data will be helpful to use this animal model more efficiently in future scientific approaches.
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