Investigative Ophthalmology & Visual Science Cover Image for Volume 61, Issue 7
June 2020
Volume 61, Issue 7
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ARVO Annual Meeting Abstract  |   June 2020
Developing chemically-induced cone degeneration models in the thirteen-lined ground squirrel
Author Affiliations & Notes
  • Hannah M Follett
    Ophthalmology & Visual Sciences, Medical College of Wisconsin, Wisconsin, United States
  • Alexander E Salmon
    Cell Biology, Neurobiology, & Anatomy, Medical College of Wisconsin, Wisconsin, United States
  • Benjamin S Sajdak
    Medical Engineering, Morgridge Institute for Research, Wisconsin, United States
  • Hanmeng Zhang
    Ophthalmology & Visual Sciences, Medical College of Wisconsin, Wisconsin, United States
  • Jenna Cava
    Ophthalmology & Visual Sciences, Medical College of Wisconsin, Wisconsin, United States
  • Mina Gaffney
    Ophthalmology & Visual Sciences, Medical College of Wisconsin, Wisconsin, United States
  • Dana K Merriman
    Department of Biology, University of Wisconsin Oshkosh, Wisconsin, United States
  • Joseph Carroll
    Ophthalmology & Visual Sciences, Medical College of Wisconsin, Wisconsin, United States
    Cell Biology, Neurobiology, & Anatomy, Medical College of Wisconsin, Wisconsin, United States
  • Footnotes
    Commercial Relationships   Hannah Follett, None; Alexander Salmon, None; Benjamin Sajdak, None; Hanmeng Zhang, None; Jenna Cava, None; Mina Gaffney, None; Dana Merriman, None; Joseph Carroll, AGTC (F), MeiraGTX (C), MeiraGTX (F), OptoVue (F), Translational Imaging Innovations (I)
  • Footnotes
    Support  NIH Grant U24EY029891, NIH Grant UL1TR001436, FFB PPA-0641-0718-UCSF. Thomas M. Aaberg, Sr. Retina Research Fund, Alcon Research Institute
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 194. doi:
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      Hannah M Follett, Alexander E Salmon, Benjamin S Sajdak, Hanmeng Zhang, Jenna Cava, Mina Gaffney, Dana K Merriman, Joseph Carroll; Developing chemically-induced cone degeneration models in the thirteen-lined ground squirrel. Invest. Ophthalmol. Vis. Sci. 2020;61(7):194.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To demonstrate chemically-induced cone degeneration in the cone-dominant thirteen-lined ground squirrel (13-LGS).

Methods : Twenty-four (12M, 12F) 13-LGS received either iodoacetic acid (IAA, n=6), adenosine triphosphate (ATP, n=6), or sodium nitroprusside (SNP, n=12) in one eye via intravitreal injection (at varying doses). An equal volume of PBS was injected in the contralateral eye of all 24 animals as a control. OCT was used to assess retinal lamination at baseline, and 1, 3, 7, 14, and 21 days after administration. AOSLO images of the cone mosaic were obtained at baseline and 7, 14, or 21 days after injection depending on the length of follow-up for each animal.

Results : Five of six animals showed severe retinal disruption as soon as 3 days after IAA, rendering AOSLO and OCT imaging and analysis impossible thereafter. No OCT abnormalities were seen in the contralateral PBS-injected eyes. With ATP, no disruptions in the outer retinal layers were observed on OCT and no cone mosaic abnormalities were seen with AOSLO. The effects of SNP were highly variable. None of the animals receiving the lowest doses (n=4) showed any damage on OCT or AOSLO, neither in the injected nor the control eye. However, at higher doses, 5 of 8 SNP eyes showed moderate to severe disruption of the photoreceptor bands with OCT and extensive cone degeneration with AOSLO in the injected eye. One of the contralateral PBS-injected eyes also showed severe damage, and the other four control eyes showed subtle to moderate disruption on OCT (which recovered in two eyes). Despite OCT recovery, pronounced cone mosaic abnormalities remained visible with AOSLO in one of these animals, as well as in one animal with normal OCT (Figure 1). The percentage of abnormal cones ranged from 5.4-7.1%.

Conclusions : Intravitreal injections of IAA, ATP, and SNP showed variable levels of cone degeneration in the 13-LGS. The lack of any effect of ATP contrasts with prior results in other species.a,b The pan-retinal degeneration following the IAA injections may be too severe for testing cell or organoid transplants. The cause of the cone mosaic abnormalities in contralateral control eyes is unknown but could be due to systemic effects of the SNP.
a PMID: 19180669
b PMID: 25425300

This is a 2020 ARVO Annual Meeting abstract.

 

Figure 1: AOSLO darkfield image of cone mosaic abnormalities in a retina with normal-appearing OCT. Scale=20µm

Figure 1: AOSLO darkfield image of cone mosaic abnormalities in a retina with normal-appearing OCT. Scale=20µm

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