Diabetes: a potential enhancer of retinal injury in rat retinas.
This study was performed to determine whether early diabetes accelerates retinal neuronal cell death and inhibits neurite regeneration. Five of ten rats were rendered diabetic with streptozotocin injection. After 3 weeks of diabetes, retinas were isolated and retinal explants were cultured in serum-free media. On day 6, the number of neurites was counted in retinal explants obtained from control and diabetic rat retinas. To identify neuronal cells undergoing apoptosis, retinas were fixed, cryosections prepared, and TdT-dUTP terminal nick-end labeling (TUNEL) was performed. Furthermore, the expression of Bax was determined in the retinas by immunohistochemistry and Western blot analysis. The number of TUNEL-positive cells in the ganglion cell layer of diabetic retinas was significantly increased (144.8+/-33.6% of control, p<0.01) compared to those in non-diabetic control rats. The number of regenerating neurites in the retinal explants of diabetic rats was significantly reduced (63.2+/-25.1% of control, p<0.05). In retinal neuronal cells of the diabetic retinas, proapoptotic Bax expression determined by immunohistochemistry and Western blot analysis showed a significant increase compared to the non-diabetic control retinas (158.1+/-55.2% of control, p<0.01; 161.6+/-48.8% of control, p<0.01, respectively). The findings indicate that diabetes upregulates Bax expression, accelerates retinal neuronal cell death, and inhibits neurite regeneration in rat retinas. Thus, it is likely that Bax dependent pathways may be activated in injured neuronal cells of the diabetic retinas.
Oshitari
Toshiyuki
T
Departments of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Roy
Sayon
S
D000818:Animals; D017209:Apoptosis; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology*; D013311:Streptozocin; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D013311:Streptozocin