Abstract
Purpose::
To introduce and correlate the DBA/2J-Rj substrain with age-matched C57Bl/6 control mice concerning selected glaucoma relevant parameters and to challenge the postulated role of DBA/2J mice as a model for secondary high tension glaucoma.
Methods::
Age-matched DBA/2J-Rj and C57Bl/6 (2 to 12 months) mice were investigated morphologically for changes in the anterior eye segment and optic nerve axon loss. 25 DBA/2J-Rj and 24 DBA/2J were investigated for IOP elevation from 4 to 10.5 months. At 7 months, six of the 24 DBA/2J with increasing IOP were analyzed for optic nerve damage and retinal ganglion cell (RGC) loss. The remaining mice were analyzed analogously at 10.5 months. Both strains were genotyped for two known SNPs in the Tyrp1 gene and the Gpnmb gene by MALDI-TOF-MS.
Results::
Compared to C57Bl/6, DBA2/J-Rj mice showed a significantly narrowed chamber angle caused by an anteriorly displaced ciliary muscle and no axon loss. IOP measurements showed that the DBA/2J-Rj population had a constant average IOP (15 mmHg). In DBA/2J the average IOP was constant at 8mmHg up to 7 months, than IOP constantly increased. In DBA/2J-Rj, individuals with IOP peaks up to 30 mmHg were detected, but none showed signs of an optic neuropathy, e.g. RGC loss or optic nerve axon loss. In contrast 30% of the DBA/2J mice at the age of 10.5 months showed a severe optic neuropathy and RGC loss. Individual IOP elevation in DBA/2J was always correlated with an iris tumor, but no stringent correlation between elevated IOP and glaucomatous changes was found. Both strains were heterozygous for the G976A SNP in Tyrp1. The point mutation C447T in Gpnmb described for DBA/2J (causing a premature stop in the Gpnmb-protein) was not detected in DBA/2J-Rj.
Conclusions::
The Tyrp 1 gene defect in connection with the narrow angle situation in DBA2/J-Rj mice are presumably causative for an individual peak development in IOP (comparable to angle closure glaucoma). IOP peaks, however, are not causative for glaucoma development in these mice. Our DBA/2J mice results indicate no general dependency of IOP elevation and glaucoma development. We found in DBA/2J population individuals with elevated IOP but without glaucomatous changes. Thus, we postulate that individually relevant factors despite elevated IOP must contribute to the development of glaucoma in DBA/2J mice. Therefore, the DBA/2J mouse cannot solely be regarded as a model for hypertension glaucoma.
Keywords: optic nerve • anterior chamber • retina