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T Michael Nork, Alexander W Katz, Elizabeth A Hennes-Beean, Charlene B Y Kim; Suprachoroidal (SC) injection of endothelin-1 (ET-1) in rabbits: A new model of outer retinal ischemia.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1637.
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© ARVO (1962-2015); The Authors (2016-present)
To develop a model of reduced choroidal blood flow (ChBF) that is independent of intraocular pressure (IOP) elevation. ChBF is reduced by both acute and chronic IOP elevation in non-human primates (NHPs). Morphological and functional changes in retinal cones have been described in human glaucoma as well as experimental glaucoma (ExGl) in the NHP. Whether such injury is due to decreased ChBF alone or to elevated IOP is unknown.
11 rabbits were intubated and anesthetized with isoflurane. ET-1 (concentrations varying from 9.4x10^-7 M to 2.5x10^-6 M diluted with aqueous vehicle) was injected into the SC space of the right eyes using microinjectors (Clearside Biomedical, Inc.), either as a single injection of 100 µl or two injections of either 50 or 100 µl in separate locations. Vehicle alone was injected in the control left eyes. 10 to 20 minutes following the SC injections, a thoracotomy was performed and 6 million 15 µm fluorescent polystyrene microspheres were injected into the left ventricle of the heart. The eyes were fixed for 2 days. The globes were then bleached, flat mounted, and photomicrographed. Image analysis was used to locate each microsphere. Total numbers of spheres in the retina and choroid were recorded as well as regional densities in the choroid.
The mean number of total choroidal microspheres in the ET-1 eyes was 6,198±797 compared to 12,131±592 in the fellow vehicle eyes. However, in the ET-1 eyes there were marked regional differences in choroidal microsphere density varying from equivalent to the controls in some parts of the choroid to nearly complete absence of microspheres in other regions. The distribution of microspheres in the vehicle eyes was similar to that previously described (Nork et al, Arch Ophthalmol, 2006;124:860). The mean number of retinal microspheres was (101±9) in the right and (102±7) in the left eyes.
Injection of ET-1 into the SC space markedly reduces choroidal blood flow. The regional effect of ET-1 on ChBF was highly variable but using two injection injections sites and a larger volume may allow for better dispersion of the ET-1 to all parts of the SC space. Although retinal blood flow was not obviously affected by SC ET-1, the microsphere numbers were small in these merangiotic retinas. This model should prove useful for studying the effects of outer retinal ischemia independently of IOP manipulation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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