J Korean Ophthalmol Soc.  2019 Dec;60(12):1205-1215. 10.3341/jkos.2019.60.12.1205.

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

• Kim C
• Lee M
• Lee SU
• Lee SJ

• KMID: 2466172
• DOI: http://doi.org/10.3341/jkos.2019.60.12.1205

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.

Keyword

Animal model; Electroretinography; Iodoacetic acid; Retinal degeneration

MeSH Terms

Adult
Body Weight
Cell Count
Electroretinography*
Humans
Immunohistochemistry
Iodoacetic Acid
Microscopy
Microscopy, Fluorescence
Models, Animal
Paraffin
Retinal Degeneration*
Retinaldehyde*
Sex Ratio
Iodoacetic Acid
Paraffin
Retinaldehyde

Figure

• 

  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.

• 

  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).

• 

  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.

• 

  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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