Sodium iodate retinal degeneration

Summary: NaIO3-induced retinal degeneration is widely used to study cell death in AMD. This results in death of retinal pigmented epithelium followed by a secondary death of photoreceptors, similar to what is observed in Geographic Atrophy.

Model Description

Age-related macular degeneration (AMD) is the leading cause of central vision loss for people age 50 and older. This vision loss makes it harder to do most of the day-to-day activities, like driving, cooking and reading.

Sodium iodate (NaIO3)-induced retinal degeneration models have been widely used to study the cell death in AMD. Sodium iodate results in death of retinal pigmented epithelium (RPE) followed by a secondary death of photoreceptors, similar to what is observed in atrophic AMD (or geographic atrophy, GA).

Animal speciesRats, Rabbits
Method of inductionInjection of sodium iodate
Follow-up periodTypically up to 35 days
Route of compound administrationIntravitreal, topical, systemic
Read-outs1. In vivo imaging
– Fluorescein angiography for damaged area quantification;
– Optical coherence tomography for retinal thickness;
2. Functional assessment:
– Rod bipolar cell function protection.

Outcomes and Capabilities

In vivo imaging

Fluorescein angiography (rabbit; Heideleberg Spectralis). Retinal damage and protection after NaIO3 induction;  Graph of area and percentage of damage in the retina.

Fig. 1. High-resolution imaging using fluorescein angiography (FA) and quantification of Area of Damage.
Fig. 1. High-resolution imaging using fluorescein angiography (FA) and quantification of Area of Damage. A. FA images from untreated and treated (FAS inhibitor) sodium iodate (NaIO3-induced rabbits on Day 3 after induction. FAS inhibitor treated eyes show decreased retinal damage area compared to untreated. The arrow points at the drug deposit in the vitreous. B. Area of damage, expressed in pixels (left y-axis) and percentage (right y-axis). Gray = untreated eyes; Blue = FAS inhibitor treated eyes.

Retinal thickness measurements (OCT) of rabbits induced with NaIO3.

Fig. 2. Protection of retinal thickness in NaIO3 induced rabbit model in eyes treated with high dose of FAS inhibitor.
Fig. 2. Protection of retinal thickness in NaIO3 induced rabbit model in eyes treated with high dose of FAS inhibitor.  Mean retinal thickness on day 0, 7, 14, 28 and 35 after NaIO3 induction and FAS inhibitor treatment on Optical Coherence Tomography (OCT). Black = untreated; blue = low dose treated; Gray = high dose treated eyes.

Functional assessment

Rod bipolar cell function protection in NaIO3-induced retinal damage model treated with a high dose FAS inhibitor.

Fig. 3. Protection of rod bipolar cell function in NaIO3 induced rabbit model in eyes treated with high dose of FAS inhibitor.
Fig. 3. Protection of rod bipolar cell function in NaIO3-induced rabbit model in eyes treated with high dose of FAS inhibitor. Amplitude of b-wave on day 0, 7, 14, 28 and 35 after NaIO3 induction and FAS inhibitor treatment in flash electroretinograms. Black = untreated; blue = low dose treated; Gray = high dose treated eyes.

References

  • Kocab AJ, Bacellar-Galdino M, Zacks DN, Jamison JA, Van De Goor J. Inhibition of Fas with ONL 1204 provides protection in a novel rabbit model of dry AMD. 2020. ARVO annual meeting. Poster presentation.

Authors' picture