Evaluation of dosage dependent effects of subretinally administered Sodium Iodate - a new model for dry AMD?

Abstract

 

Purpose

 

Despite recent improvements in the treatment of exudative age-related macular degeneration (AMD), few effective treatments are available for non-exudative AMD, the most common subtype of the disease. This is partly because of the lack of a suitable models of non-exudative AMD and the most advanced from of this disease, geographic atrophy. Systemic administration of Sodium iodate (SoIod), that leads to a generalized toxic reaction in RPE cells have been used as a model of RPE degeneration. But, this model creates a generalized toxicity to ocular tissue that may interfere with studies focused on the treatment of RPE degeneration. Here we describe methods to create a localized area of RPE atrophy by subretinal delivery of SoIod in rabbit eyes.

 

Methods

 

With a vitrectomy-like pars plana approach, a subretinal bleb with SoIod solution wascreated in 14 pigmented rabbits with different concentrations (10mmol, n=3;1mmol, n=7; 0.1mmol n=2). In the control group (n=2) the bleb was created with BSS. The bleb was left or drained after 10 min. The animals were studied at four time points: 1 day, 4 days, 7 days and 14 days after surgery, which included fluorescein angiography, infrared and red free fundusphotography, spectral optical coherence tomography. RPE and retina histologic changes were studied light and electron microscopy.

 

Results

 

Reproducible RPE and outer retina atrophy was induced after localized exposure with SoIod by subretinal injection in all animals without choroidal or retinal neovascularization as early as 4 days after surgery. Severe damage with complete retinal atrophy was experienced in the 10mmol group. The effect of 0.1mmol SoIod was not conclusive or reproducible. OCT measurements in the 1mmol group demonstrated a decrease in retinal tissue/ RPE-complex thickness in the targeted area from mean 148um to 107umm (37.8%), which was clearly visible in vivo with infrared and red free fundusphotography. Scanning and transmission electron microscopy confirmed the corrupted retinal area indicating loss of micorvilli.

 

Conclusions

 

Our data indicate that subretinal application of 1mmol SoIod in pigmented rabbits leads to a limited and circumscribed area of atrophy of the RPE-outer retina complex similar to late stages of dry AMD. This procedure introduces a new and reliable animal model for geographic atrophy.

 

Keywords: 412 age-related macular degeneration • 637 pathology: experimental • 762 vitreoretinal surgery