Abstract
Purpose :
Loss of choroidal endothelial cells is a key pathophysiologic step in a wide range of retinal diseases, including age-related macular degeneration (AMD). Animal models of choroidal cell loss are valuable for developing and testing potential therapies. This study describes multiple methods of choroidal damage in rats, including by suprachoroidal injection of immunotoxins (antibodies conjugated to saporin (SAP), a ribosome inactivating protein) and intravenous administration of sodium iodate.
Methods :
Anti-CD38 and anti-CD105 antibodies conjugated to SAP were delivered to Sprague Dawley rat eyes via suprachoroidal injection. Sodium iodate was delivered intravenously for comparison. Different doses of SAP immunotoxins (0.05, 0.25 and 0.5 mg/ml; 10ul/eye) and sodium iodate (25, 50 and 75 mg/kg) were tested in an equal number of male and female rats. At different time points (1-, 2-, and 3-weeks) post-administration, animals were analyzed via OCT, fundus photography, and choroidal flat mounts using Lycopersicon esculentum (tomato) lectin staining.
Results :
SAP immunotoxin induced local choroidal damage by one week post-injection at the lowest dose tested (0.05 mg/kg). By contrast, the lowest dose of sodium iodate (25mg/kg) induced only minimal choroidal vascular loss at one week. Choroidal loss was localized to the injection site for suprachoroidal delivery of immunotoxin, whereas choroidal damage from sodium iodate was bilateral, widespread, and uniform (Figure 1). Both anti-CD38-SAP and anti-CD105-SAP were similarly efficient at inducing choroidal damage within the injected area. While SAP conjugates did not induce systemic toxicity, sodium iodate was fatally toxic at higher doses, and care should be taken to reduce animal loss while still achieving choroidal cell dropout.
Conclusions :
We have developed multiple methods of inducing choroidal cell loss that is readily visible on clinical imaging and immunohistochemistry. Suprachoroidal SAP causes sectoral damage ideal for studying the impact of choroidal cell loss on adjacent tissue. The sodium iodate approach has convenient systemic administration that results in uniform choroidal damage, providing a useful model to test choroidal cell replacement strategies.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.