A novel model of photoreceptor-defic1ent retina induced by subretinal injection of iodoacetate

J. C. Huang, M. Ishida, I. K. Sugino, R. Yao, M. A. Zarbin

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose. Photoreceptor (PR) transplantation may be an effective treatment for some patients with retinal degeneration. To develop PR transplantation technology, a suitable model system is needed. Methods. Sodium iodoacetate (IA) was used to abolish the PRs of cat retina, by intravenous, intravitreous. or subretinal injection. (A) Intravenous dose: 5 and 10 mg/kg over 2 consecutive days. (B) Intravitreous dose: 5, 10, 20, 50 or 500 μg/eye; IA in 100 μl of a buffer solution (BSS) was injected into the center of vitreous cavity. (C) Subretinal delivery via IA injection into the subretinal space of retinal bleb (4 mm diameter) with a dose of 0. 1, 1, 1.6, 2 or 5 μg/bleb; IA was dissolved in 50 μ1 BSS or Healon, 0.5%. Survival time was 1 - 6 weeks. Results, (A) Intravenous IA injection induced selective damage to PRs in 1 week, with different degrees of injury in different areas of the retina and in different compartments of the PRs. Other relinal cells, including retinal pigment epithelium (RPE), were spared. However, some severe neurological and hernatological side effects made the intravenous approach unacceptable. (B) Intravitreous IA injection also induced damage to PRs with doses of between 5 - 50 μg at 2 & 6 weeks. Nonetheless, the pattern and degree of PR damage varied greatly, likely due to an uneven distribution of IA in the vitreous. Total retinal degeneration was seen with the high dose of 500 μg. (C) Subretinal IA injection induced a well localized PR destruction with good preservation of RPE. Inner retinal cells were also preserved, although with some degree of inner nuclear layer thickening and inner plexiform layer vacuolation. Total PR degeneration within the retinal bleb was achieved 6 weeks after an injection of a mixture of IA (1.6, 2, or 5 μg) with Healon. The viscosity of the Healon solution may have prolonged the localization and effect of IA. When IA was dissolved in BSS. a lower degree and less consistent PR degeneration was seen. Healon or BSS alone did not induce PR damage. Conclusions. A model with PR-deficient retina has been created by subretinal injection of IA. A lesser degree of damage to the inner retina may also be induced. This model may subserve studies on retinal degeneration as well as PR transplantation.

Original languageEnglish (US)
Pages (from-to)S331
JournalInvestigative Ophthalmology and Visual Science
Volume38
Issue number4
StatePublished - 1997

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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