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Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4644-52. doi: 10.1167/iovs.14-16011.

Development of Animal Models of Local Retinal Degeneration.

Author information

1
Hansen Experimental Physics Laboratory, Stanford University, Stanford, California, United States 2Department of Ophthalmology, Stanford University, Stanford, California, United States 3Institut de la Vision, Paris, France.
2
Department of Ophthalmology, Stanford University, Stanford, California, United States.
3
Santa Cruz Institute for Particle Physics, University of California, Santa Cruz, California, United States.
4
Hansen Experimental Physics Laboratory, Stanford University, Stanford, California, United States 5Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.
5
Hansen Experimental Physics Laboratory, Stanford University, Stanford, California, United States 2Department of Ophthalmology, Stanford University, Stanford, California, United States.
6
Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah, Salt Lake City, Utah, United States.

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-μm 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.

PMID:
26207299
PMCID:
PMC4516014
DOI:
10.1167/iovs.14-16011
[Indexed for MEDLINE]
Free PMC Article

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