Abstract
Purpose :
Macular degeneration is one of the leading causes of blindness in people over the age of 50; the most common being age-related macular degeneration. The pathology can include hyperreflective foci (HRF) detected by spectral-domain optical coherence tomography (SD-OCT) in association with sub-retinal pigment epithelium (RPE) drusen and hyper-pigmentation. Sodium iodate (SI) rapidly induces retinal degeneration in mice that involves RPE pathology modeling some of the characteristics of macular degeneration. The purpose of this study was to determine whether the sodium iodate-induced pathology includes elevated expression of vimentin in the RPE, as well as HRF and other pigmentary changes.
Methods :
Twenty C57BL/6J young adult male mice were injected with SI dissolved in PBS at 15, 30, 45, or 60 mg/kg. SD-OCT (Bioptigen) images were acquired pre-injection, and 1, 3, 5, and 7 days post-injection Retinal thickness was measured using Bioptigen software and HRF were counted manually. Frozen vertical retinal cross-sections (12 µm thick) of eyes were processed for H&E staining and IHC. Tissue from each group was also processed for electron microscopy (EM).
Results :
HRFs were detected by SD-OCT in the retinas of mice given 30, 45, and 60 mg/kg SI, but not those given 15 mg/kg SI. HRFs were visible as early as post-injection day 1, and became more distinct by day 7. The higher doses of SI caused retinal thickness to be significantly decrease by day 5 post-injection compared to control (p>0.001). H&E images showed that the 15mg/kg dose had no apparent effect compared to the control, whereas sections from mice treated with 30, 45, and 60mg/kg contained pigmented lesions in the neural retina. The pigmented lesions in the IS/OS layer and the ONL were also detected by EM. Vimentin expression was increased in the RPE layer of the retina in a dose-dependent manner, detected by IHC.
Conclusions :
The results suggest that SI induces HRF and pigment migration into the neural retina of mice. Furthermore, the SI-induced expression of vimentin in the RPE layer suggests a change in phenotype consistent with endothelial to mesenchymal transition (EMT). Overall, the results suggest a causal link between HRF, hyperpigmentation and EMT of RPE cells.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.