Abstract
Purpose :
Glaucoma is the leading cause of irreversible blindness worldwide. Despite this, a complete understanding of the disease and its pathogenesis remains a struggle due to the lack of high fidelity spontaneous polygenetic models that recapitulate the human phenotype. In recent years, the BXD mouse family has emerged as a source of spontaneous models of ocular disease. It is the purpose of this study to identify natural polygenetic mouse models of primary open angle (POAG), primary angle closure (PACG), and normotensive (NTG) glaucoma by mining the BXD family and provide them as a valuable resource for the vision research community.
Methods :
BXD strains were selected by evaluating data from previous studies that include the density of dead axons, ON damage scorings, and IOP. Eight strains were selected for further study. Functional/anatomical analyses including optical coherence tomography (OCT), optokinetic nystagmus (OKN), full field and pattern electroretinograms (ERG/PERG), and IOP measurements were performed every 3 months from the age of 1 month to 12 months. Gonioscopy was performed at 12 months to determine if the angle was open or closed. Histological and ultrastructural analyses of the eye/optic nerve will be performed after euthanasia at 12 months.
Results :
Although this study is still in progress, preliminary data highlight BXD50 and BXD51 as possible models of POAG. Both strains exhibit open angles, decreased ERG and PERG amplitudes, and loss of contrast sensitivity by 12 months. Interestingly, the two strains vary greatly in IOP over their lifetimes with BXD50 reaching a maximum IOP of 28 mmHg, while the maximum IOP of BXD51 was 41 mmHg.
Histological analysis of the eye/optic nerve is in progress to evaluate optic nerve damage and RGC health.
Conclusions :
The BXD family of mice offers valuable insights into ocular disease pathogenesis. Of the strains we selected, BXD50 and BXD51 present POAG-like phenotypes. Ongoing studies are being performed to better characterize plausible spontaneous models of PACG and NTG, thereby providing additional valuable tools for the future study of glaucoma.
This is a 2021 ARVO Annual Meeting abstract.