Magnetic resonance imaging indicates decreased choroidal and retinal blood flow in the DBA/2J mouse model of glaucoma

Animal models of glaucoma often use ocular hypertension as the foundation for studying anatomic changes, physiological regulation, and disease mechanisms.1,2 One widely used model is the DBA/2J mouse.3–5 This mouse has mutations that cause expression of two aberrant proteins: tyrosinase-related protein 1 (Tyrp1), which causes iris stromal atrophy,6 and glycoprotein transmembrane nmb (Gpnmb), thought to cause iris pigmentary dispersion, which increases intraocular pressure (IOP) by obstructing the trabecular meshwork and decreasing trabecular outflow facility.7 The DBA/2J mouse develops ocular hypertension and optic neuropathy at the age of 4 to 6 months. It is unknown whether the ocular hypertension impairs ocular blood flow (BF) in the DBA/2J mouse and contributes to the optic neuropathy. MRI allows for the study of anatomy, blood flow, and responses to stimulations (so-called functional MRI) in a noninvasive manner without depth limitation or image aberrations caused by tissue density variations that hinder optical methods. MRI is popular in neuroscience research, particularly to image brain anatomy and functional responses to sensory or cognitive stimuli. In addition, BF can be quantitatively measured with an MRI technique called arterial spin labeling (ASL).8,9 The resolution of these MRI modalities is sufficient for studying small organs and tissues, including those of the mouse eye.10 Given this MRI capability and the lack of information about ocular BF in the DBA/2J mouse, this study sought to test the hypothesis that ocular BF is reduced in the DBA/2J mouse over the time course of its development of ocular hypertension and optic neuropathy. Age-matched C57BL/6 mice were used as controls, as in other DBA/2J studies.11,12