Sodium iodate selectively injuries the posterior pole of the retina in a dose-dependent manner: morphological and electrophysiological study

Abstract

Sequential morphological and functional features of retinal damage in mice exposed to different doses (40 vs. 20 mg/kg) of sodium iodate (NaIO(3)) were analyzed. Retinal morphology, apoptosis (TUNEL assay), and function (electroretinography; ERG) were examined at several time points after NaIO(3) administration. The higher dose of NaIO(3) caused progressive degeneration of the whole retinal area and total suppression of scotopic and photopic ERG. In contrast, the lower dose induced much less severe degeneration in peripheral part of retina along with a moderate decline of b- and a-wave amplitudes in ERG, corroborating the presence of regions within retina that retain their function. The peak of photoreceptor apoptosis was found on the 3rd day, but the lower dose induced more intense reaction within the central retina than in its peripheral region. In conclusion, these results indicate that peripheral area of the retina reveals better resistance to NaIO(3) injury than its central part.

Fig. 1

Representative images visualizing histopathological changes within the central part of the retina recorded 1 (c), 7 (d, e), and 28 (f) days after NaIO₃ injection in both the higher and lower doses; (a, b) saline-treated control mice. Retinal morphology was analyzed in the whole eye flat mounts (FMs) with RPE nuclei pseudocolored blue and green indicating RPE autofluorescence (a and d) as well as in H/E stained sections (b, c, e, and f). The black arrow (f) indicates glial (Műller) cells phagocyting melanine remnants. GCL ganglion cell layer, INL inner nuclear layer, ONL outer nuclear layer

Fig. 2

The regional pattern of retinal damage after the injection of the lower dose (20 mg/kg) of sodium iodate (a). TUNEL-stained sections visualizing apoptotic photoreceptors located in the central (b) and peripheral (e) parts of the retinal area on the 3rd day post NaIO₃ exposure. (c, f) corresponding (central vs. peripheral part) H/E stained sections. (d, g) corresponding (central vs. peripheral part) whole eye flat mounts (FMs) with nuclei pseudocolored blue; green pseudocolor indicates RPE autofluorescence. The black arrow (c) indicates a thin layer of melanin released along Bruch’s membrane. The graphs illustrate the difference in the number of apoptotic cells between the central and peripheral parts of the retina exposed to the lower (h) and higher (i) doses of NaIO₃. Photoreceptor apoptosis shows the peak intensity on the 3rd day after NaIO₃ administration regardless of the dose used. GCL ganglion cell layer, INL inner nuclear layer, ONL outer nuclear layer

Fig. 3

A comparison of outer nuclear layer thickness (μm; mean ± SD) at the different time points after NaIO₃ administration at the higher (40 mg/kg) and lower (20 mg/kg) dose. a The central part of the retina (posterior pole), approx. 300 μm from the optic nerve head. b The peripheral part of the retina, approx. 300 μm from the ora serrata. * P < 0.05 lower versus higher dose

Fig. 4

ERG responses recorded at different time points after NaIO₃ administration in the higher dose (40 mg/kg). a saline-treated control mice. b ERG recorded on the 1st day after sodium iodate delivery. c ERG recorded on the 3rd day after sodium iodate injection. d The b-wave amplitude measurements on the 1st, 3rd, 7th, 18th, and 28th day after NaIO₃ administration (μV; mean ± SD). From the 3rd day after NaIO₃ injection, both the scotopic and photopic responses were abolished and became undetectable. * P < 0.05 versus control

Fig. 5

A comparison of the b-wave and a-wave amplitudes after NaIO₃ injection in the higher (40 mg/kg) and lower (20 mg/kg) doses over time. The higher dose suppressed the ERG response completely from the 3rd day post sodium iodate delivery while the lower concentration of NaIO₃ led to a moderate decline in the a- and b-wave under both scotopic and photopic conditions. The results are presented as mean ± SD