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bioRxiv · 10.1101/2025.07.29.667466

Development of a Targeted Choroidal Injury Model for the Study of Retinal Degenerations and Therapeutic Cell Replacement

Pandala, N.·De Melo Haefeli, L.·Lang, M.·Stone, E. M.·Tucker, B. A.·Mullins, R. F.·Han, I. C.
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Abstract

PurposeChoroidal loss is an important pathophysiological step in many retinal diseases, but few reliable translational models of choroidal injury exist. Here, we report a new targeted choroidal injury model using bioconjugated saporins and compare it models of systemic sodium iodate administration. MethodsWild-type Sprague-Dawley rats were given suprachoroidal injections of anti-CD38 or anti-CD105 antibodies conjugated to saporin immunotoxin (10 {micro}l at 0.05 {micro}g/{micro}L) to induce selective choroidal endothelial cell injury. These animals were compared to wild-type rats given sodium iodate (75 mg/kg) via tail vein injections, with a dose escalation study (25, 50, and 75 mg/kg) in immunocompromised (Sprague-Dawley Rag2/Il2g double-knockout) rats. Animals were examined at 1-, 2-, and 3-weeks post-treatment, and the degree of choroidal injury compared using fundus photography, optical coherence tomography, and immunohistochemistry. ResultsSuprachoroidal administration of anti-CD38 or anti-CD105 saporins resulted in severe choroidal vascular injury localized to the injection site, without damage to adjacent choroidal vasculature, progressive injury over time, or development of choroidal neovascularization. By contrast, sodium iodate treated animals had rapid, diffuse choroidal loss which progressed throughout the study time points, with fatal systemic side effects at the highest (75 mg/kg) dose. ConclusionsSuprachoroidal injection of anti-CD38 and anti-CD105 saporins results in targeted, localized, non-progressive choroidal injury in rats. These models offer alternatives to systemic sodium iodate administration, which causes diffuse, progressive choroidal injury. Translational RelevanceImmunotoxin-based models of targeted choroidal injury may be useful for understanding pathways of retinal degeneration and facilitating development of therapies for diseases involving choroidal cell loss.

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Pandala, N., De Melo Haefeli, L., Lang, M., Stone, E. M., Tucker, B. A., Mullins, R. F., Han, I. C.. 2025-08-01. Development of a Targeted Choroidal Injury Model for the Study of Retinal Degenerations and Therapeutic Cell Replacement. https://doi.org/10.1101/2025.07.29.667466

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