Detection of localized retinal malfunction in retinal degeneration model using a multielectrode array system.
Light stimulation inhibits the retinal dark current through phototransduction signals in the photoreceptors. Electroretinography (ERG) detects the blockage of the dark current as the a-wave of the ERG. However, standard ERGs represent the summed neural activity of the retina, and information on localized functions cannot be obtained. In this study, we used a multielectrode array (MEA) system and directly recorded the focal activities of the photoreceptors of the retina. Retinas were isolated from dark-adapted rodents and were draped over the electrode array with vitreal surface of the retina on the electrode array. After light stimulation, negative waves were recorded from each electrode. Adding aminobutyric acid, a selective agonist of mGluR6 expressed on ON-bipolar cells, to the media did not block the generation of the responses. The amplitude of the response increased with increasing retinal development. When the retina was locally injured, light-elicited responses were diminished only in the injured areas of the retina. Retinas isolated from rats given N-methyl-N-nitrosourea (MNU) were also tested. In central retinas of MNU-treated rats, the responses were progressively decreased following injection of MNU. In contrast, in the peripheral retinas, amplitude of the responses was relatively retained, consistent with the retinal thickness observed by immunohistochemistry. In conclusion, light-evoked responses were recorded with the MEA system. The MEA system was useful for detecting subtle and focal activation of photoreceptors. This spatial information should be valuable in investigating local functional recovery in therapeutically treated areas, such as in gene transfer or cell transplantation.
Homma
Kohei
K
Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Chou-ku, Kobe, Japan.
Osakada
Fumitaka
F
Hirami
Yasuhiko
Y
Jin
Zi-Bing
ZB
Mandai
Michiko
M
Takahashi
Masayo
M
D000477:Alkylating Agents / Q000633:toxicity; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D004596:Electroretinography / Q000295:instrumentation* / Q000379:methods*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008027:Light; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008770:Methylnitrosourea / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008839:Microelectrodes / Q000592:standards; D010775:Photic Stimulation; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism; D012162:Retinal Degeneration / Q000175:diagnosis* / Q000503:physiopathology*; D014785:Vision, Ocular / Q000187:drug effects / Q000502:physiology
D000477:Alkylating Agents; D000613:Aminobutyrates; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; C113897:metabotropic glutamate receptor 6; D008770:Methylnitrosourea