Development of animal models of local retinal degeneration

Henri Lorach, Jennifer Kung, Corinne Beier, Yossi Mandel, Roopa Dalal, Philip Huie, Jenny Wang, Seungjun Lee, Alexander Sher, Bryan William Jones, Daniel Palanker

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

PURPOSE. Development of nongenetic animal models of local retinal degeneration is essential for studies of retinal pathologies, such as chronic retinal detachment or age-related macular degeneration. We present two different methods to induce a highly localized retinal degeneration with precise onset time, that can be applied to a broad range of species in laboratory use. METHODS. A 30-mm thin polymer sheet was implanted subretinally in wild-type (WT) rats. The effects of chronic retinal separation from the RPE were studied using histology and immunohistochemistry. Another approach is applicable to species with avascular retina, such as rabbits, where the photoreceptors and RPE were thermally ablated over large areas, using a high power scanning laser. RESULTS. Photoreceptors above the subretinal implant in rats degenerated over time, with 80% of the outer nuclear layer disappearing within a month, and the rest by 3 months. Similar loss was obtained by selective photocoagulation with a scanning laser. Cells in the inner nuclear layer and ganglion cell layer were preserved in both cases. However, there were signs of rewiring and decrease in the size of the bipolar cell terminals in the damaged areas. CONCLUSIONS. Both methods induce highly reproducible degeneration of photoreceptors over a defined area, with complete preservation of the inner retinal neurons during the 3-month follow-up. They provide a reliable platform for studies of local retinal degeneration and development of therapeutic strategies in a wide variety of species.

Original languageEnglish
Pages (from-to)4644-4652
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume56
Issue number8
DOIs
StatePublished - Jul 2015

Bibliographical note

Publisher Copyright:
© 2015 The Association for Research in Vision and Ophthalmology, Inc.

Keywords

  • AMD
  • Animal model
  • Geographic atrophy

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