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Jeffrey Kiel, Saurav B Chandra, Kaiwalya S Deo, Eric Muir, Timothy Q Duong; Dorzolamide effects on retinal and choroidal blood flow in a mouse glaucoma model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):696.
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© ARVO (1962-2015); The Authors (2016-present)
Dorzolamide (DZ) is a carbonic anhydrase inhibitor used in glaucoma patients to lower intraocular pressure (IOP). The goal of this study is to determine the effect of topical DZ application on retinal (RBF) and choroidal blood flow (ChBF) in DBA/2J (DBA) mice, an established model of glaucoma.
Male wild-type (WT) C57BL/6J mice aged 4 months (n=8), and male DBA mice aged 4 months (n=7) and 9 months (n=6) were used for this in vivo MRI study. The mice were anesthetized with 1-1.2% isoflurane. Temperature was maintained at 37°C and respiratory rate at 80-110 bpm. MRI scans were performed in a 7T magnet (Bruker Biospec) with a 150 Gauss/cm gradient using a custom eye coil for imaging (ID=0.6 cm) and a heart coil for ASL (ID=0.8 cm). The scans were acquired with a GE-EPI sequence with FOV=0.6x0.6cm, matrix=144x144 zero-filled interpolation to 256x256, 400 μm coronal slice, 2 shots, labeling duration=2.94s, TR=3s, and TE=9.8ms. Scan were made just before and at 1 and 2 hr after topical DZ (5 μl, 2%).
Basal ChBF was similar in the 4-mo DBA mice and the 4-mo WT, but basal ChBF in the 9-mo DBA/2J mice was lower than WT (p<0.01) and 4-mo DBA (p<0.05). At 1-hour post DZ, blood flow tended to increase in all animal groups, although the increase was significant only in the 9-mo DBA ChBF and in the 4-mo WT RBF. At 2 hrs post DZ, ChBF dropped slightly below baseline, except for ChBF in the 9-mo DBA, which remained elevated. The RBF followed similar patterns except that at 2 hrs post DZ, RBF in the 4- and 9-mo DBA mice remained elevated.
The DBA mouse develops increasing IOP with age. This should reduce perfusion pressure, and thus ChBF and RBF. The results show this expected age-dependent decrease in basal ChBF and RBF, consistent with our previous study. At 1-hr post DZ, ChBF and RBF increased significantly or trended higher in all groups, possibly due to decreased IOP (and increased perfusion pressure) or perhaps due to a direct vasodilatory effect of DZ. This effect is transient for ChBF in the young WT and DBA mice, but more sustained in the older DBA mice. Future studies will determine the effects of chronic DZ treatment on ChBF and RBF in DBA mice.
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