Caspase-dependent retinal ganglion cell apoptosis in the rat model of acute diabetes
- Author:
- No author available
- Journal Title:
- CHINESE MEDICAL JOURNAL
- Issue:
- 24
- DOI:
- No doi available
- Key Word:
- - retinal ganglion cell;apoptosis;diabetic retinopathy
Abstract： Background Neural apoptosis is generally believed to be mediated by two distinct pathways, caspase-dependant and caspase-independent pathways. This study investigated the apoptotic pathways involved in retinal ganglion ceils in acute diabetes in rats. Methods Diabetes was induced in male Wistar rats by a peritoneal injection of streptozotocin (STZ). Expression and localization of caspase-3 and apoptosis-inducing factor (AIF) proteins in the retina of diabetic rats was examined by Western blotting and immunohistochemistry analyses. Terminal transferase dUTP nick end labeling (TUNEL) assay and immunofluorescent staining specific for caspase-3 and AIF were applied to analyze for apoptosis of retinal ganglion cells. In addition, a caspase-3 inhibitor DEVD-CHO was injected intravitreally to further determine the apoptotic pathways of retinal ganglion cells triggered in acute diabetes. Results Two weeks after induction of diabetes, a significant increase in caspase-3 protein expression and localization occurred in the nerve fiber layer, ganglion cell layer, and inner plexiform layer of the retina. Four weeks after the onset of diabetes, the increase in caspase-3 expression was profound eight weeks postinduction of diabetes (P＜0.05). Meanwhile, no AIF protein expression was detected in this study. In addition, intravitreal administration of the caspase-3 inhibitor DEVD-CHO reduced apoptosis of retinal ganglion cells by its direct inhibitory action on caspase-3. Conclusion Caspase-dependent apoptotic pathways may be the main stimulant of STZ-induced retinal ganglion cell apoptosis in acute diabetes.
- [1]Zhang X,Kiechle FL.Apoptosis: biochemical aspects and clinical implications.[J].2002,326(1).
- [2]K, Holopigian,V C, Greenstein,W, Seiple,etc.Evidence for photoreceptor changes in patients with diabetic retinopathy.[J].1997,38.
- [3]Barber AJ,Antonetti DA,Kern TS,etc.The Ins2Akita Mouse as a Model of Early Retinal Complications in Diabetes.[J].2005,46(6).
- [4]Missotten L,Abu-El-Asrar AM,Geboes K,etc.Expression of antiapoptotic and proapoptotic molecules in diabetic retinas.[J].2007,21(2).
- [5]A A, Dosso,F, Yenice-Ustun,J, Sommerhalder,etc.Contrast sensitivity in obese dyslipidemic patients with insulin resistance.[J].1998,116.
- [6]Barber AJ.A new view of diabetic retinopathy: a neurodegenerative disease of the eye.[J].2003,27(2).
- [7]J M, BLOODWORTH.Diabetic retinopathy.[J].1900,11.
- [8]Van Ells TK,Ganapathy V,Smith SB,etc.Death of retinal neurons in streptozotocin-induced diabetic mice.[J].2004,45(9).
- [9]P, Chaudhary,F, Ahmed,P, Quebada,etc.Caspase inhibitors block the retinal ganglion cell death following optic nerve transection.[J].1999,67.
- [10]Hancock HA,Kraft TW.Oscillatory potential analysis and ERGs of normal and diabetic rats.[J].2004,45(3).
- [11]Van Gurp M,Martin SJ,Saelens X,etc.The role of mitochondrial factors in apoptosis: a Russian roulette with more than one bullet.[J].2002,9(10).
- [12]Takahashi M,Ono Y,Sumioka K,etc.Induction of a 55-kDa PKN cleavage product by ischemia/reperfusion model in the rat retina.[J].2000,41(1).
- [13]SVEND ERIK SIMONSEN.The Value of the Oscillatory Potential in Selecting Juvenile Diabetics at Risk of Developing Proliferative Retinopathy[J].1980,58(6).
- [14]Deary IJ,Frier BM,Ewing FM,etc.Seeing beyond retinopathy in diabetes: electrophysiological and psychophysical abnormalities and alterations in vision.[J].1998,19(4).
- [15]Kern TS,Mohr S,Tang J,etc.Caspase activation in retinas of diabetic and galactosemic mice and diabetic patients.[J].2002,51(4).
- [16]Vingrys AJ,Fletcher EL,Phipps JA.Paired-flash identification of rod and cone dysfunction in the diabetic rat.[J].2004,45(12).
- [17]A Possible Participation of Advanced Glycation End Products in the Development of the Early Phase of Diabetic Retinopathy Yasunori Segawa,Yutaka Shirao,Sho-ichi Yamagishi,etc.A Possible Participation of Advanced Glycation End Products in the Development of the Early Phase of[J].1998,30(6).
- [18]Stefanis L.Caspase-dependent and -independent neuronal death: two distinct pathways to neuronal injury.[J].2005,11(1).
- [19]Roumier T,Kroemer G,Ravagnan L.Mitochondria, the killer organelles and their weapons.[J].2002,192(2).
- [20]Yamamoto S,Oshitari T,Roy S,etc.Mitochondria- and caspase-dependent cell death pathway involved in neuronal degeneration in diabetic retinopathy.[J].2008,92(4).
- [21]Lieth E,Buchanan AG,Gardner TW,etc.Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin.[J].1998,102(4).