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

Authors

Narendra Pandala, Lorena De Melo Haefeli, Mallory Lang, Edwin M Stone, Robert F Mullins, Budd A Tucker, Ian C Han

Published in

Translational vision science & technology. Volume 15. Issue 8. Pages 17. Aug 03, 2026.

Abstract

Loss of the choroid is an important pathophysiological step in retinal diseases ranging from age-related macular degeneration (AMD) to choroideremia. However, current models of choroidal injury, such as laser photocoagulation-induced injury, induce acute tissue damage that does not parallel the gradual loss seen in most retinal degenerations. As such, there remains a need for models of targeted choroidal injury to study mechanisms of disease and develop potential treatments.
We report a targeted choroidal injury model using bioconjugated saporins (immunotoxins) against cluster of differentiation (CD) domains CD38 and CD105. To induce injury, 10 µL of bioconjugate solution or control (phosphate-buffered saline) was delivered via suprachoroidal injection in wild-type Sprague-Dawley (SD) and Sprague-Dawley Rag2/Il2rg (SRG; double-knockout) rats. The extent and severity of choroidal injury were compared with animals treated with sodium iodate administered via tail vein injections at 1, 2, and 3 weeks post-treatment using clinical imaging and immunohistochemistry.
Choroidal injury induced by either anti-CD38 or anti-CD105 immunotoxin was targeted to the choroid and localized to the sector of the injection, unlike global destruction induced by sodium iodate. Immunotoxin-induced vascular damage remained constant over 3 weeks, without choroidal neovascularization seen, whereas sodium iodate caused progressive and severe injury of the choroid and overlying retina.
Suprachoroidal injection of anti-CD38 and anti-CD105 immunotoxins can induce localized and durable choroidal injury in both wild-type and immunosuppressed rats.
Immunotoxin-based models of targeted choroidal injury may be useful for understanding pathophysiologic mechanisms and developing therapies in conditions involving choroidal cell death.

PMID:
42622344
Bibliographic data and abstract were imported from PubMed on 20 Aug 2026.

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