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

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

doi:10.1167/tvst.15.8.17

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

Journal article

Open access

Peer reviewed

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

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

Translational vision science & technology, Vol.15(8), 17

08/03/2026

DOI: 10.1167/tvst.15.8.17

PMID: 42622344

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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.

Immunohistochemistry

Animals

Choroid - drug effects

Choroid - injuries

Choroid - pathology

Disease Models, Animal

Iodates - toxicity

Male

Rats

Rats, Sprague-Dawley

Retinal Degeneration - pathology

Retinal Degeneration - therapy

Details

Title: Subtitle: Development of a Targeted Choroidal Injury Model for the Study of Retinal Degenerations and Therapeutic Cell Replacement
Creators: Narendra Pandala - University of Iowa
Lorena De Melo Haefeli - University of Iowa, The University of Iowa Institute for Vision Research
Mallory Lang - University of Iowa
Edwin M Stone - University of Iowa
Robert F Mullins - University of Iowa
Budd A Tucker - University of Iowa
Ian C Han - University of Iowa
Resource Type: Journal article
Publication Details: Translational vision science & technology, Vol.15(8), 17
DOI: 10.1167/tvst.15.8.17
PMID: 42622344
NLM abbreviation: Transl Vis Sci Technol
ISSN: 2164-2591
eISSN: 2164-2591
Publisher: Association for Research in Vision and Opthalmology
Language: English
Date published: 08/03/2026
Academic Unit: The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; John and Marcia Carver Nonprofit Genetic Testing Laboratory; Neuroscience and Pharmacology; Ophthalmology and Visual Sciences
Record Identifier: 9985219922002771

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