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Generating Retinal Injury Models in Xenopus Tadpoles
Published on: October 13, 2023
Development of a Targeted Choroidal Injury Model for the Study of Retinal Degenerations and Therapeutic Cell
Narendra Pandala1, Lorena De Melo Haefeli1, Mallory Lang1
1Institute for Vision Research and Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, USA.
Purpose:
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.
Methods:
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.
Results:
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.
Conclusions:
Suprachoroidal injection of anti-CD38 and anti-CD105 immunotoxins can induce localized and durable choroidal injury in both wild-type and immunosuppressed rats.
Translational Relevance:
Immunotoxin-based models of targeted choroidal injury may be useful for understanding pathophysiologic mechanisms and developing therapies in conditions involving choroidal cell death.
