De Melo Haefeli, L. | bioRxiv Science

bioRxiv2025

Acriflavine delivery via Polyurethane nanocapsules to treat neovascular age-related macular degeneration

Choroidal neovascularization is a complication associated with retinal diseases such as age-related macular degeneration (AMD), a leading cause of vision loss in the developed world. Choroidal neovascular membrane (CNVM) refers to the abnormal growth of blood vessels in the retina which results in exudation and/or hemorrhage, leading to photoreceptor damage and vision loss. Currently first-line treatment for CNVM include intravitreal injections of vascular endothelial growth factor (VEGF)-binding antibodies that prevent the growth of these leaky blood vessels. Unfortunately, anti-VEGF drugs often require frequent injections, and prolonged VEGF inhibition has been associated with retinal atrophy and decreased long term effectiveness in some patients. This study presents the use of Acriflavine, a small molecule HIF1 inhibitor loaded polyurethane nanocapsules to treat CNVM in a rat model. Fourteen days following laser injury and intravitreal drug administration, CMVM size was significantly reduced in acriflavine nanocapsule and free acriflavine treated animals as compared to drug free controls. Moreover, acriflavine nanocapsules reduce CNVM incidence compared to drug free controls by approximately 25%. Among the different delivery routes tested, intravitreal delivery of acriflavine nanocapsules was found to be superior to subretinal and suprachoroidal delivery for reducing CNVM area without causing significant damage to the neural retina. This paper presents the synthesis, characterization and the effectiveness of the polyurethane based acriflavine delivery system in treating choroidal neovascularization.

pharmacology and toxicology↗

bioRxiv2025

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

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.

neuroscience↗