A new model of retinal photoreceptor cell degeneration induced by a chemical hypoxia-mimicking agent, cobalt chloride.
Retinal photoreceptor cell degeneration was induced by cobalt chloride, a chemical hypoxia-mimicking agent in rodents. Time course and dose-response of photoreceptor cell degeneration in mouse retina after intravitreal injection of cobalt chloride were examined by conventional histological analysis by hematoxylin and eosin staining and in situ terminal dUTP-biotin nick end labeling of DNA fragments (TUNEL) method with the use of paraffin-embedded sections. The dose-response of photoreceptor cell degeneration in rat retina was also examined. Photoreceptor cells progressively degenerated with time and under dose-response relationship. The suitable dose of cobalt chloride for the selective photoreceptor cell degeneration in mice is 10-12 nmol intravitreal injection at the volume of 2 microl. The retinal morphology of the mice 2 weeks after the 10-12 nmol intravitreal injection was similar to that of retinal degeneration in the mutant rd mouse. Retinal damage of total retinal layers was induced by an excessive dose of cobalt chloride. The progression of retinal damage after cobalt chloride injection, measured morphologically, was completed at 1 week. However, nuclear DNA fragmentation, mainly detected at outer nuclear layer by TUNEL, peaked at 48 h after 12 nmol cobalt chloride injection. Thus, the selective photoreceptor cell degeneration induced by cobalt chloride follows DNA fragmentation at outer nuclear layer. The photoreceptor cell degeneration is established optionally by cobalt chloride without use of the retinal degeneration mutant animals. Thus, we have described the development of a new model of retinal photoreceptor cell degeneration induced by a chemical hypoxia-mimicking agent.
Hara
Akira
A
Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. ahara@cc.gifu-u.ac.jp
Niwa
Masayuki
M
Aoki
Hitomi
H
Kumada
Masako
M
Kunisada
Takahiro
T
Oyama
Takeru
T
Yamamoto
Tetsuya
T
Kozawa
Osamu
O
Mori
Hideki
H
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D003035:Cobalt; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D051379:Mice; D010786:Photoreceptor Cells / Q000187:drug effects / Q000473:pathology*; D012162:Retinal Degeneration / Q000139:chemically induced* / Q000473:pathology*; D013997:Time Factors
D003035:Cobalt; C018021:cobaltous chloride