Third-order neuronal responses contribute to shaping the negative electroretinogram in sodium iodate-treated rats.
OBJECTIVE
To determine possible mechanisms that shape the negative electroretinograms (ERGs) in rats with photoreceptor degeneration induced by destruction of the retinal pigment epithelium.


METHODS
Sprague-Dawley rats (n = 48) were injected intravenously with 60 mg/kg of sodium iodate (NaIO(3)). Full-field ERGs were elicited by different stimulus intensities with a maximum luminance of 1.23 log cd-s/m(2) and recorded at 6 hr and on days 7, 14, and 28 after the NaIO(3) injections. DL-2-amino-4-phosphonobutyric acid (APB, 1 mM) or N-methyl-L-aspartic acid (NMDA, 5 mM) was injected into the vitreous cavity to isolate photoreceptor (PIII), second-order, and third-order neuronal responses. After recording the ERGs, animals were sacrificed for histological analysis.


RESULTS
Negative ERGs were recorded under scotopic conditions on day 7 after the NaIO(3) injection. An intravitreal injection of NMDA eliminated most of the a-wave, resulting in the abolition of the negative ERG. On days 14 and 28, the a-wave amplitudes were reduced compared to those on day 7 with the loss of the negative ERGs. The mean amplitudes of the PIII and second-order neuronal responses were progressively reduced until day 7. In contrast, the mean amplitude of the third-order neuronal responses were relatively well-preserved until day 7 and then were decreased between days 7 and 14. As a result, the amplitude of the third-order neuronal response dominated over the second-order neuronal response on day 7. There was no significant difference in the middle and inner retinal morphology at each time point.


CONCLUSIONS
NaIO(3) produced negative ERGs transiently, and the third-order neuronal responses were the main contributors to the negative ERG. The relative preservation of the third-order neuronal response plays a role in shaping the negative ERGs in this model.
Tanaka
Michiko
M
Department of Ophthalmology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan.
Machida
Shigeki
S
Ohtaka
Kouji
K
Tazawa
Yutaka
Y
Nitta
Junfuku
J
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D007275:Injections, Intravenous; D007452:Iodates / Q000494:pharmacology*; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000503:physiopathology*; D013997:Time Factors
D007452:Iodates; C032285:sodium iodate