Involvement of calpain isoforms in retinal degeneration in WBN/Kob rats.
Results of our recent studies in rats suggested that calpains play an important role in retinal cell death induced by ischemia-reperfusion in vivo and by hypoxia in vitro. Study of spontaneous animal models could help determine the involvement of calpains in human retinopathy. The WBN/Kob rat is such a model for spontaneous retinal degeneration. The purpose of the study reported here was to determine the involvement of calpain isoforms during retinal degeneration in WBN/Kob rats. Histologic and functional retinal degeneration in WBN/Kob rats was observed by use of light microscopy and electroretinography, respectively. Proteolysis of alpha-spectrin in the retina was detected by use of immunoblot analysis in aging WBN/Kob rats. This proteolysis was associated with the increases of retinal calcium content and caseinolytic activity for calpains 1 and 2. Expression of calpain 1, calpain 2, and calpastatin mRNAs in the retina, as measured by use of reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, were only slightly up-regulated at 24 weeks of age. In contrast, expression of retina-specific calpains, such as Rt88, Rt88', and Rt90 mRNA, was markedly down-regulated at 12 weeks of age. Expression of calpain 10 mRNA in the retina was only slightly down-regulated at 12 weeks of age. In contrast to mRNA expression, various expression patterns of calpain 10 proteins were observed. Increased retinal calcium content, leading to activation of calpains 1 and 2, may be an important event in the sequential changes leading to degeneration of the retina in WBN/Kob rats. Activated calpain causing proteolysis of alpha-spectrin and changes in Rt88, Rt88', Rt90 and calpain 10 may also contribute to retinal degeneration.
Azuma
Mitsuyoshi
M
Research Laboratories, Senju Pharmaceutical Co. Ltd., 1-5-4, Murotani, Nishiku, Kobe, Hyogo, 651-2241, Japan.
Sakamoto-Mizutani
Kanako
K
Nakajima
Takeshi
T
Kanaami-Daibo
Sayaka
S
Tamada
Yoshiyuki
Y
Shearer
Thomas R
TR
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002154:Calpain / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004596:Electroretinography; D007527:Isoenzymes; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012160:Retina / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D012162:Retinal Degeneration / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013049:Spectrin / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D002135:Calcium-Binding Proteins; D007527:Isoenzymes; D012333:RNA, Messenger; D013049:Spectrin; C033668:calpastatin; D002154:Calpain