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Kim, Lee, Lee, and Lee: Electroretinography Changes in Feline Model of Iodoacetic Acid-induced Retinal Degeneration
Original Article

Journal of the Korean Ophthalmological Society 2019; 60(12): 1205-1215.

Published online: 17 December 2019

DOI: https://doi.org/10.3341/jkos.2019.60.12.1205

Electroretinography Changes in Feline Model of Iodoacetic Acid-induced Retinal Degeneration

Changzoo Kim, MD1, Myungshin Lee, MD1, 2, Seung Uk Lee, MD, PhD1, Sang Joon Lee, MD, PhD1

1Department of Ophthalmology, Kosin University College of Medicine, Busan, Korea.

2Department of Ophthalmology, Inje University College of Medicine, Busan, Korea.

Address reprint requests to Sang Joon Lee, MD, PhD. Department of Ophthalmology, Kosin University Gospel Hospital, #262 Gamcheon-ro, Seo-gu, Busan 49267, Korea. Tel: 82-51-990-6140, Fax: 82-51-990-3026, hhiatus@gmail.com

Received 4 July 2019       Revised 9 August 2019       Accepted 29 November 2019

©2019 The Korean Ophthalmological Society

The Korean Ophthalmological Society

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

We explored changes in photoreceptor function and histology in an iodoacetic acid (IAA)-induced model of feline retinal degeneration.

Methods

From January to October 2014, we studied 11 adult felines (22 eyes) over 2 years of age divided into two groups (two in a control and nine in an IAA group). The mean body weights of these two groups were 1.75 ± 0.35 and 1.61 ± 0.19 kg, and the male:female sex ratios 1:1 and 2:7, respectively. Electroretinograms (ERGs) were obtained before injection and at 1–4 week post-injection (20 mg/kg IAA). Standard paraffin retinal sections were stained with hematoxylin/eosin and other sections subjected to immunohistochemistry. We histologically evaluated the outer nuclear layer, and photoreceptor cone and rod cells.

Results

In ERGs of the IAA group, both the rod and cone mean b wave amplitudes decreased significantly from week 1 to week 4 after injection (27.43, 29.41, 64.17, and 56.03; and 61.04, 51.25, 131.36, and 136.68 µV, respectively) compared to baseline (322.48 and 610.00 µV respectively) (p < 0.01). Optical microscopy revealed a significant decrease in the cell count of the outer nuclear retinal layer (16.83 ± 0.89 in the control and 11.98 ± 3.55 in the IAA groups, p < 0.01). Fluorescence microscopy revealed a significant reduction in the mean area per unit length of the rod cell layer (35,225.67 ± 2,477.02 and 14,903.62 ± 2,319.65 in the control and IAA groups, p < 0.01), but not in the cone cell count (26.16 ± 1.34 and 23.98 ± 6.16 in the control and IAA groups, p = 0.075).

Conclusions

ERGs revealed that functional b wave amplitudes fell after IAA-induce retinal degeneration in felines; histology showed that this was accompanied by reductions in the numbers of outer nuclear layers and rod cells. IAA induces photoreceptor degeneration in felines; further study is necessary.

Keywords: Animal model, Electroretinography, Iodoacetic acid, Retinal degeneration

Figures and Tables

Figure 1

A schematic of the left-eye feline fundus showing the locations and sizes of histological tissue samples. A = superiorly, the average distance between the pars plicata and pars plana; B = laterally, the average distance between the pars plicata and pars plana; C = Inferiorly, the average distance between the pars plicata and pars plana; D = medially, the average distance between the pars plicata and pars plana; E = superiorly, the average distance between the pars plana and ora serrata; F = laterally, the average distance between the pars plana and ora serrata; G = inferiorly, the average distance between the pars plana and ora serrata; H = medially, the average distance between the pars plana and ora serrata; I = the average distance from the superior optic disc margin to the superior ora serrata; J = the average distance from the lateral optic disc margin to the lateral ora serrata; K = the average distance from the inferior optic disc margin to the inferior ora serrata; L = the average distance from the medial optic disc margin to the medial ora serrata; M = the average distance from the superior optic disc margin to the superior tapetum lucidum; N = the average distance from the lateral optic disc margin to the lateral tapetum lucidum; O = the average distance from the inferior optic disc margin to the inferior tapetum lucidum.

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Figure 2

A representative electroretinogram (ERG) scotopic response at 0.1 cd·s/m2 of feline #5 (right eye). (A) The scotopic ERG wave was below 0.1 cd·s/m2 from baseline (before iodoacetic acid [IAA] injection) to 4th week after injection. The b wave disappeared at 1st week after injection, and did not reappear during the next 3 weeks. (B) Changes in the average b wave amplitude (cd·s/m2) after IAA injection. The differences were statistically significant (*p < 0.05, Wilcoxon signed-rank test).

jkos-60-1205-g002
Figure 3

The mean ONL nuclear cell count and the mean RHO-stained area were significantly reduced after IAA injection; however, neither the INL nuclear cell count nor the L/M opsin cell count fell (A–D). INL = inner nuclear layer; IAA = iodoacetic acid; ONL = outer nuclear layer; L/M = anti-red/green; RHO = rhodopsin. *p < 0.05 Wilcoxon signed-rank test.

jkos-60-1205-g003
Figure 4

Iodoacetic acid (IAA) triggered loss of the outer but not the inner nuclear layer. (A, C–F) Control group histology (no IAA injection, [A], H&E staining, ×400; [C–F], IHC staining, ×400). (B, G–J) IAA group histology 4 weeks after IAA injection [B], H&E staining, [G–J], IHC staining, ×400). Scale bar indicated 50 µm.

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Table 1

Gross anatomical lengths

jkos-60-1205-i001

Values are presented as mean ± standard deviation.

A = superiorly, the average distance between the pars plicata and pars plana; B = laterally, the average distance between the pars plicata and pars plana; C = inferiorly, the average distance between the pars plicata and pars plana; D = medially, the average distance between the pars plicata and pars plana; E = superiorly, the average distance between the pars plana and ora serrata; F = laterally, the average distance between the pars plana and ora serrata; G = inferiorly, the average distance between the pars plana and ora serrata; H = medially, the average distance between the pars plana and ora serrata; I = the average distance from the superior optic disc margin to the superior ora serrata; J = the average distance from the lateral optic disc margin to the lateral ora serrata; K = the average distance from the inferior optic disc margin to the inferior ora serrata; L = the average distance from the medial optic disc margin to the medial ora serrata; M = the average distance from the superior optic disc margin to the superior tapetum lucidum; N = the average distance from the lateral optic disc margin to the lateral tapetum lucidum; O = the average distance from the inferior optic disc margin to the inferior tapetum lucidum.

Table 2

Baseline characteristics of the felines

jkos-60-1205-i002

Values are presented as mean ± standard deviation unless otherwise indicated.

IAA = iodoacetic acid; M/F = male/female.

Table 3

Average ERG b wave amplitudes after iodoacetic acid injection

jkos-60-1205-i003

Values are presented as mean ± standard deviation unless otherwise indicated.

ERG = electroretinogram.

*Based on the Wilcoxon signed-rank test; †statistically significant (p < 0.05); ‡baseline/weekly amplitude ratio (percentage); §intensity:photopic response = 3.0 cd·s/m2.

Table 4

Average ERG b wave latency after iodoacetic acid injection

jkos-60-1205-i004

Values are presented as mean ± standard deviation.

ERG = electroretinogram.

*Based on the Wilcoxon signed-ranked test; †statistically significant (p < 0.05); ‡intensity:photopic response = 3.0 cd·s/m2.

Notes

Conflicts of Interest The authors have no conflicts to disclose.

Appendix

Appendix 1

Anti-red/green (L/M) opsin data (A, B). The control cone cell outer segment unit length (26.11 ± 9.09 units) was significantly greater than that of the iodoacetic acid group (13.21 ± 4.32 units) (p < 0.01).

jkos-60-1205-a001

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