Retinal Changes in an ATP-Induced Model of Retinal Degeneration
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Date
2016-04
Journal Title
Journal ISSN
Volume Title
Publisher
Frontiers
Abstract
In rodents and felines, intravitreal administration of adenosine triphosphate (ATP) has been shown to induce photoreceptor death providing a tractable model of retinal
degeneration in these species. This study investigated the long term effects of
photoreceptor loss in an ATP induced feline model of retinal degeneration. Six normal
sighted felines were unilaterally blinded using intravitreal ATP injections and assessed
using electroretinography (ERG) and optical coherence tomography (OCT). At 30 h
(n = 3) or 12 weeks (n = 3) post-injection, the animals were euthanized and the
eyes enucleated. Retinae were sectioned and labeled using immunohistochemistry for
markers of cell death, neural remodeling and gliosis. Ongoing cell death and retinal
degeneration was observed in the outer retina at both 30 h and 12 weeks following
unilateral ATP injection. Markers of mid to late-stage retinal remodeling such as cell
displacement and aberrant neurite growth were observed in the inner retina at 12 weeks
post-injection. Ganglion cells appeared to remain intact in ATP injected eyes. Müller cell
gliosis was observed throughout the inner and outer retina, in some parts completely
enveloping and/or displacing the surviving neural tissue. Our data suggests that the
ATP injected feline retina continues to undergo progressive retinal degeneration and
exhibits abnormalities consistent with a description of retinal remodeling commonly seen
in other models of retinal degeneration. These findings validate the use of intravitreal ATP injection in feline as a large animal model of retinal degeneration which may aid in development of therapies aiming to restore visual function after photoreceptor degeneration.
Description
Keywords
Retina, Gliosis, Animal models, Adenosine triphosphate, Retinal degeneration, Feline, Photoreceptor cells, Retinitis pigmentosa
Citation
Aplin, F., K. Vessey, C. D. Luu, R. Guymer, R. K. Shepherd, and E. L. Fletcher. 2016. Retinal Changes in an ATP-Induced Model of Retinal Degeneration. Frontiers in neuroanatomy. 10: 46.