A Swine Model of Selective Geographic Atrophy of Outer Retinal Layers Mimicking Atrophic AMD: A Phase I Escalating Dose of Subretinal Sodium Iodate.

Abstract

PURPOSE:

To establish the dose of subretinal sodium iodate (NaIO3) in order to create a toxin-induced large animal model of selective circumscribed atrophy of outer retinal layers, the retinal pigment epithelium (RPE), and photoreceptors, by spectral-domain optical coherence tomography (SD-OCT) and immunocytochemistry.

METHODS:

Fifteen male and female healthy Yorkshire pigs received unilateral subretinal escalating doses of NaIO3 under general anesthesia. In all the animals, volumes of 0.1 to 0.2 mL NaIO3 were injected into the subretinal space of the area centralis through a 23/38-gauge subretinal cannula. Control SD-OCTs were performed 1 and 2 months after the surgery, at which time pigs were euthanized and eyes enucleated. Globes were routinely processed for histologic and immunohistochemical evaluation.

RESULTS:

Spectral-domain OCT and immunohistochemistry revealed circumscribed and well-demarcated funduscopic lesions, limited to the outer retinal layers in pigs treated with 0.01 mg/mL subretinal sodium iodate.

CONCLUSIONS:

The swine model of a controlled area of circumscribed retinal damage, with well-delimited borders, and selectively of the outer layers of the retina presented herein shows several clinical and histologic features of geographic atrophy in AMD. Therefore, it may represent a valuable tool in the investigation of new emerging regenerative therapies that aim to restore visual function, such as stem cell transplantation or optogenetics.

• Authors: Jordi Monés, Marta Leiva, Teresa Peña, Gema Martínez, Marc Biarnés, Miriam Garcia, Anna Serrano, Eduardo Fernandez
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 57 Issue 10 Pg. 3974-83 (08 01 2016) ISSN: 1552-5783 [Electronic] United States
• PMID: 27479813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Iodates
• sodium iodate

Topics

• Animals
• Anterior Eye Segment (diagnostic imaging)
• Biomarkers (metabolism)
• Diagnosis, Differential
• Disease Models, Animal
• Disease Progression
• Female
• Fluorescein Angiography
• Follow-Up Studies
• Fundus Oculi
• Geographic Atrophy (metabolism, pathology)
• Immunohistochemistry
• Iodates (metabolism)
• Male
• Ophthalmoscopy (methods)
• Retinal Degeneration (diagnosis)
• Retinal Pigment Epithelium (pathology)
• Subretinal Fluid (chemistry)
• Swine
• Tomography, Optical Coherence (methods)
• Visual Acuity