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Silja Hansen, Anne Louise Askou, Toke Bek, Morten de la Cour, Thomas Corydon; A novel method to induce experimental subretinal neovascularization in the pig in vivo. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1040.
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Current treatment of exudative age-related macular degeneration (eAMD) aims at antagonizing vascular endothelial growth factor (VEGF), an established driver of choroidal neovascularization (CNV). However, the need for repetitive injections increases the risk of adverse effects. Ocular gene therapy targeting VEGF has shown great potential in a murine model for CNV and application in a porcine model would be a major step towards clinical translation. Previous models in pigs using laser for the CNV induction have caused damage to the neuroretina due to thermic burns. Furthermore, neovascularization was mainly induced from the retina, which is not the site of origin of CNV in eAMD. Therefore, we developed a method to overcome these challenges by introducing a protective subretinal injection of saline prior to the laser application initiating the CNV.
In the left eye of 12 pigs a serous detachment was induced by injecting 0,05 ml saline using a subretinal cannula (Poly Tip Cannula 23/28g). Subsequently, a laser burn (810 nm, spot size 600 mm, 1 W for 1 sec.) focussed on Bruchs membrane was applied in the area of the detached neuroretina. The right eye was treated with laser without retinal detachment. The effect was evaluated by opthalmoscopy, optical coherence tomography (OCT), OCT-angiography and fluoresceinangiography (FA) in vivo and histology after subsequent enucleation.
For eyes treated with laser combined with retinal detachment, the neuroretina was undamaged and CNV formation was observed by OCT in 90% (9/10), of which (50%) had FA leakage at day 7. For eyes treated with laser alone, CNV formation was observed in 90% (9/10) of the cases, but neuroretinal damage was observed in 100% of these eyes.
Laser induced experimental CNV in pigs can be produced with a high success rate, and neuroretinal damage can be prevented by a serous retinal detachment. This technique may be valuable for reducing the growth of CNV by downregulating VEGF synthesis by gene therapy.
This is a 2020 ARVO Annual Meeting abstract.
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