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Adam Hanif, Moe Aung, Megan Prunty, Hanna Park, P. Michael Iuvone, Machelle T Pardue; Regulating arachidonic acid metabolites ameliorates neurovascular defects and subsequent visual deficits in STZ rats. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal functional hyperemia (FH) occurs in response to light stimulation, and is hypothesized to be mediated by arachidonic acid metabolites like epoxyeicosatrienoic acid (EET). Recent studies have reported decreases in retinal FH response in patients with pre-clinical diabetic retinopathy. In this study, we investigated how selectively inhibiting EET degradation with AUDA [12-(3-adamantan-1-yl-ureido) dodecanoic acid (5 mg/kg)] might mediate retinal FH, and influence visual function in a rat model of type-1 diabetes.
Hyperglycemia was induced using streptozotocin (STZ; 100 mg/kg). Control (CTRL) and diabetic (DM) rats were divided amongst four groups: CTRL + Vehicle (n=6), CTRL + AUDA (n=9), DM + Vehicle (n=14), and DM + AUDA (n=5). After one week of established diabetes, DM groups were injected with either AUDA or vehicle solution daily. CTRL rats received daily injections of their respective solutions at matched time points. Flicker-induced FH was assessed 2 weeks after the start of injections. At 4 and 6 weeks, groups were assessed for visual function with optokinetic tracking and for cataract formation with a slit lamp. CTRL + AUDA and CTRL + Vehicle groups were found to be statistically indistinguishable from one another, and are therefore grouped together and presented as “CTRL”.
DM + Vehicle rats exhibited significantly less flicker-induced retinal arteriole vasodilation than CTRLs (p<0.05) two weeks post-STZ. However, daily injection of AUDA in DM rats maintained arteriolar vasodilation at levels significantly greater than DM + Vehicle rats (p<0.008). Treatment with AUDA delayed the onset of visual deficits compared to DM + Vehicle groups, and significantly preserved contrast sensitivity up to six weeks after onset of diabetes (p<0.01). Cataract scores between DM groups treated with vehicle or AUDA were not statistically different, though both were significantly greater than those of CTRLs.
Defects in retinal FH appeared two weeks prior to the first signs of diabetes-related visual deficit. Interestingly, our findings indicated that early regulation of arachidonic acid metabolism could preserve FH response, and delay visual decline in diabetic animals. Early treatment of abnormal retinal FH response in diabetic patients may be an effective intervention in vision loss associated with diabetic retinopathy.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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