Purchase this article with an account.
W. Lavery, E. R. Muir, J. W. Kiel, R. C. Renteria, T. Q. Duong; MRI Reveals Decreased Retinal and Choroidal Blood Flow in a Mouse Model of Glaucoma (DBA/2J). Invest. Ophthalmol. Vis. Sci. 2010;51(13):5036.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Glaucoma, a leading cause of irreversible blindness worldwide, is characterized by a progressive degeneration of retinal ganglion cells and the optic nerve. Glaucoma is often associated with elevated intraocular pressure (IOP). A longstanding hypothesis is that the elevated IOP exerts a compressing force on the blood vessels, reducing blood flow (BF) to the retina and the optic nerve. DBA/2J mice develop an optic neuropathy similar to glaucoma. The present study employs magnetic resonance imaging (MRI) to examine the hypothesis that glaucoma is mediated by dysregulation of ocular blood flow in this mouse model.
Depth-resolved quantitative BF MRI (42x42x400µm) was performed on 6-month old DBA/2J glaucomatous mice (considered to be mid-stage of the disease, n= 5) and controls (C57BL6 strain, n= 6) under 1.2% isoflurane anesthesia with IACUC approval. BF images were acquired with echo-planar imaging using a novel arterial spin labeling MRI technique and a custom-made eye coil at 7 Tesla. The MRI parameters were: 6x6 mm field of view, 144x144 matrix, a single 0.4 mm slice, 2 shots, 2.94 s labeling pulse, 3.0 s repetition time, and 13 ms echo time. BF maps were calculated. Automated profile analysis was performed to average layer-specific BF along the length of the retina.
BF MRI unambiguously quantifies choroidal and retinal BF. In normal animals, choroidal BF was 4.2±1.0mL/g/min (mean±SD, n=6), and retinal BF was 0.94±0.19 mL/g/min. The choroidal BF was 4.4 times higher than retinal BF (P < 0.0001), consistent with those reported using radioactive microsphere technique in rat retinas and previously reported MRI BF from our laboratory. In the glaucomatous eyes of the DBA/2J mice (n=5), the choroidal BF was 1.5±0.8mL/g/min and retinal BF was 0.61±0.18mL/g/min. Both choroidal (P<0.001) and retinal BF (P<0.02) were statistically significantly different between normal and glaucomatous retinas.
This study, to our knowledge, is the first report of quantitative resolution of retinal and choroidal BF using MRI. Both retinal and choroidal BF values were lower in DBA/2J compared to control mice, consistent with the hypothesis that ischemia may play a role in this mouse model of glaucoma. Future studies will investigate basal BF and BF responses to stimulations as a function of disease progression. MRI has the potential to offer depth-resolved, quantitative BF data that may prove useful for glaucoma disease staging and therapeutic drug testing.
This PDF is available to Subscribers Only