Sodium iodate-induced retina and choroid damage model in rabbits to test efficacy of RPE auto-transplants

Abstract

Purpose : Age-related Macular Degeneration (AMD) is a blinding disease that is initiated by RPE dysfunction and cell death, which then leads to both photoreceptor cell death and atrophy of the choriocapillaris. Sodium iodate (NaIO3) can damage the choroid, RPE, and retina. Here, we analyzed NaIO3-treated rabbits as a potential model to test the efficacy of human induced pluripotent stem (iPS) cell-derived retinal pigment epithelium (RPE) auto-transplants.

Methods : Pigmented rabbits were intravenously injected (n=18) with 2 ml of NaIO3 diluted in saline, (concentration range 0-17.6 mg/kg). All rabbits were analyzed using indocyanine green and fluorescein angiography (ICGA and FA) along with optical coherence tomography (OCT), obtained with the Spectralis device (Heidelberg Engineering). Rabbits were enucleated (n=16) at 1, 2, 3, and 4 week time points. Histological assessment of damage was achieved by H&E staining and immunohistochemistry.

Results : Intravenous injection of >11mg/kg sodium iodate consistently produced long-lasting, but patchy damage inferior to the horizontal equator and/or posterior pole. Damage was apparent in the choroid and retina within 24 hours after injection. FA exhibited sharply demarcated leakage in late frames between the optic disc and the posterior pole, suggesting loss of RPE barrier function. Inferior to the horizontal equator, FA showed complete signal blockage while late-phase ICGA showed hyporeflectivity. In SD-OCT’s enhanced depth imaging mode, this area corresponded to an intact RPE band with loss of choroidal vascular reflectivity. The above modalities combined to suggest severe choriocapillaris non-perfusion inferior to the posterior pole. These findings were corroborated with histology, whereby the inner choroid showed a fibrin band on H&E.

Conclusions : In a combined FA/ICG and SD-OCT analysis we demonstrate loss of RPE barrier function along with severe choriocapillaris non-perfusion within 24h of >11mg/kg NAIO3 injection. NaIO3-injected rabbits provide a potential model to test the efficacy of iPS-cell derived RPE auto-transplants to rescue retinal and choroidal damage in a non-immune privileged environment, owing to the loss and dysfunction of host RPE.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.