A rat model of choroidal ischemia

Abstract

Purpose : Choroidal ischemia has been associated with a spectrum of retinopathies including age-related macular degeneration and retinitis pigmentosa. It was overlooked as a symptom rather than the cause of the mentioned diseases until recently. Therefore, an animal model of choroid ischemia would be helpful for further studies to better understand the contribution of the vasculature in the choroid membrane. We hypothesize that suprachoroidal injecting NaIO₃, which was previously described to induce retinal atrophy, would induce choroid atrophy in rats and mimic human pathological choroid ischemia.

Methods : We injected 1 μL of 10 mg/mL NaIO₃ into the Specific pathogen-free (SPF) grade Sprague Dawley male rat (N = 24) suprachoroidal space with a micro syringe and observed for up to 90 days, during which fundus angiography/indocyanine angiography (FA/ICG, N=8), choroid thickness (N=8) and fluorescence imaging of the blood vessels(N=8) were assessed and compared with clinical images. The blood vessel junction density of different time points was calculated with FA/ICG image processed by AngioTool. The choroid thickness was measured with H&E staining of the eye sections (n=24 for each eye). Immunofluorescence staining was done with an anti-CD34 antibody. Unpaired t-test and one-way ANOVA were used for statistical analysis.

Results : Results showed that 7 days after suprachoroidal injection of NaIO₃ would result in local choroid atrophy and the atrophy lasted for 90 days, where the choroid thickness decreased by half (p<0.0005) and the choriocapillaris lost its original density and structure. The vessel junction density also decreased significantly compared to healthy controls(p<0.0005). The FA/ICG images were comparable between rat choroid ischemia and human dry AMD patients where a dark ischemic region was evident. The retinal vessels remained intact together with the inner plexiform layer.

Conclusions : Our results suggested the rat choroid ischemia model resembles human choroid ischemia and the ischemia is limited to the choroid layer. This unveiled new angles for further study of retinopathy and choroidopathy.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.