Intravenous Sodium Iodate Administration Induces Macula-Specific RPE Damage and Rod-Dominant Apoptosis in the Cynomolgus Monkey

Purpose Although sodium-iodate (SI)–induced retinal degeneration has been extensively studied in rodent models, its macular pathology and cone/rod vulnerability difference remains elusive. This study aims to characterize SI-induced macular pathology in cynomolgus monkeys. Methods Intravenous injections of SI were performed on four male cynomolgus monkeys including three young adults (Animal No. 1–3; five to six years old) and one juvenile (Animal No. 4; two years old) from a breeding colony. To optimize dosing, Animal No. 1 received 25 and 37.5 mg/kg SI; Animal No. 2 received a single SI dose (30 mg/kg) to confirm reproducibility. Animal No. 3 was used to examine subclinical effects at a lower dose (25 mg/kg). Animal No. 4 received increasing doses (30, 35, and 40 mg/kg). Retinal changes were evaluated using fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT). Histological analysis and transmission electron microscopy (TEM) were also performed. Results In Animal No. 1, prominent fluorescein leakage by FA and RPE elevation on OCT was observed in the macula after 37.5 mg/kg SI. Histology and TEM revealed that elevated RPE lesion was accompanied by significant RPE migration. Animal No. 2 exhibited similar retinal degeneration. Animal No. 3 exhibited no RPE barrier disruption but showed outer segment damage and RPE melanolipofuscin accumulation. Animal No. 4 showed minimal macular degeneration despite escalating doses. In the peripheral retina, rod apoptosis was evident, whereas macular cone cell death was limited even at high doses. Conclusion Systemic SI administration can induce macular degeneration with RPE barrier disruption in young-adult monkeys, supporting a macula- and cell-type–specific vulnerability.

• Publication year

  2025

• Venue

  Investigative Ophthalmology and Visual Science

• Publication date

  2025-07-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1167/iovs.66.9.18PMID 40626808PMCID 12248985
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Lamp2 Deficiency Enhances Susceptibility to Oxidative Stress–Induced RPE Degeneration

  2025cited by this paper
• Design and Characterization of a Novel Intravitreal Dual-Transgene Genetic Medicine for Neovascular Retinopathies

  2024cited by this paper
• Peripapillary Retinal Nerve Fiber Layer and Macular Ganglion Cell-Inner Plexiform Layer Parameters and Their Associated Factors in Cynomolgus Macaques.

  2024cited by this paper
• Pharmacokinetic and Target Engagement Measures of ANX007, an Anti-C1q Antibody Fragment, Following Intravitreal Administration in Nonhuman Primates

  2023cited by this paper
• Nonhuman Primate Eyes Display Variable Growth and Aging Rates in Alignment With Human Eyes

  2023cited by this paper
• Biology and postnatal development of organ systems of cynomolgus monkeys (Macaca fascicularis)

  2022cited by this paper
• Fine Tuning of an Oxidative Stress Model with Sodium Iodate Revealed Protective Effect of NF-κB Inhibition and Sex-Specific Difference in Susceptibility of the Retinal Pigment Epithelium

  2021cited by this paper
• Sodium iodate induces ferroptosis in human retinal pigment epithelium ARPE-19 cells

  2021cited by this paper
• Normative Data of Ocular Biometry, Optical Coherence Tomography, and Electrophysiology Conducted for Cynomolgus Macaque Monkeys

  2021cited by this paper
• Irreversible Photoreceptors and RPE Cells Damage by Intravenous Sodium Iodate in Mice Is Related to Macrophage Accumulation.

  2018cited by this paper
• Absolute and estimated values of macular pigment optical density in young and aged Asian participants with or without age-related macular degeneration

  2017cited by this paper
• Sodium Iodate Produces a Strain-Dependent Retinal Oxidative Stress Response Measured In Vivo Using QUEST MRI

  2017cited by this paper
• Retinal pigment epithelial cell necroptosis in response to sodium iodate

  2016cited by this paper
• Expression and distribution of peroxiredoxins in the retina and optic nerve

  2015cited by this paper
• Direct effect of sodium iodate on neurosensory retina.

  2014cited by this paper
• Animal models of age-related macular degeneration and their translatability into the clinic

  2014cited by this paper
• Role of Unfolded Protein Response Dysregulation in Oxidative Injury of Retinal Pigment Epithelial Cells

  2014cited by this paper
• Sodium iodate induced retinal degeneration: new insights from an old model

  2014cited by this paper
• Receptor interacting protein kinase mediates necrotic cone but not rod cell death in a mouse model of inherited degeneration

  2012cited by this paper
• Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis

  2010cited by this paper
• Sodium Iodate Selectively Injuries the Posterior Pole of the Retina in a Dose-Dependent Manner: Morphological and Electrophysiological Study

  2010cited by this paper
• Peroxiredoxin 3 (PDRX3) is highly expressed in the primate retina especially in blue cones.

  2008cited by this paper
• Behavioral and anatomical abnormalities in a sodium iodate-induced model of retinal pigment epithelium degeneration.

  2006cited by this paper
• Morphologic characteristics of retinal degeneration induced by sodium iodate in mice

  2002cited by this paper
• Relocalization of apoptosis-inducing factor in photoreceptor apoptosis induced by retinal detachment in vivo.

  2001cited by this paper
• The effect of sodium iodate and melanin on the formation of glyoxylate.

  1992cited by this paper
• EXPERIMENTAL PIGMENTARY DEGENERATION OF THE RETINA BY SODIUM IODATE

  1941cited by this paper

• No citing papers are available for this paper.