Bcl-2 In Retina Research Articles

Nimodipine inhibits N-methyl-N-nitrosourea-induced retinalphotoreceptor apoptosis in vivo

Purpose:The purpose of the present study was to investigate the effect of nimodipine (NMD), a calcium channel blocker, on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration.Materials and Methods:60 mg/kg MNU was given intraperitoneally to 6-week-old female Sprague-Dawley rats, and NMD was injected intraperitoneally for up to 5 days after MNU. The effect of NMD was evaluated by electron microscopy and electroretinography (ERG). Proteins of Bax, Bcl-2, Caspase-3, and mitochondrial membrane potential (MMP) were analyzed with flow cytometry. The expressions of phosphodiesterase (PDE) and Caspase-3 were detected by reverse transcriptase polymerase chain reaction (RT-PCR).Results:The apparent preservation of NMD to the photoreceptor cell was demonstrated by electron microscopy. After NMD treatment, both a- and b-waves of ERG were significantly higher compared with the control group, and had a protective effect on MNU-damaged retinal ERG. Flow cytometric assays showed that NMD decreased the level of Bax and Caspase-3 and increased the activity of Bcl-2 in retina. NMD significantly restored the mitochondrial membrane potential (MMP). RT-PCR analysis demonstrated that NMD treatment significantly decreased mRNA level of Caspase-3, and mRNA level of PDE was clearly upregulated.Conclusions:These data suggest that NMD may regulate the expressions of Bax, Bcl-2, Caspases-3, and PDE, and protection on the functions of retinal cell mitochondria inhibit MNU-induced photoreceptor cell apoptosis and protect retinal function in rats.

Effects of minocycline on expression of bcl-2, bax in early retinal neuropathy of diabetes in rats.

To study the effect of the minocycline (MNC) on expression of bcl-2, bax in retinal nerve cells of rat with diabetes. Male SD rats were randomly divided into negative control group, model control group and MNC treated group. Diabetes model was established by intraperitoneal injection of 60 mg/kg streptozotocin (STZ). The protein expressions of bcl-2 and bax in retina were detected by immunohistochemistry method. Compared with the negative control group, bax immunoreactive neurons in retina were increased significantly (P<0.01) in model control group. However, bax immunoreactive neurons in retina in MNC treated group were significantly decreased (P<0.01). Compared with the model control group, bcl-2 immunoreactive neurons in retina were increased significantly(P<0.01) in MNC treated group. MNC can obviously decreased expression of bax and increased expression of bcl-2 in retina with DR. It is one of path of inhibiting impairment on retinal nerve cells with DR.

Overexpression of Bcl-2 in Vascular Endothelium Inhibits the Microvascular Lesions of Diabetic Retinopathy

Recent studies on the pathogenesis of diabetic retinopathy have focused on correcting adverse biochemical alterations, but there have been fewer efforts to enhance prosurvival pathways. Bcl-2 is the archetypal member of a group of antiapoptotic proteins. In this study, we investigated the ability of overexpressing Bcl-2 in vascular endothelium to protect against early stages of diabetic retinopathy. Transgenic mice overexpressing Bcl-2 regulated by the pre-proendothelin promoter were generated, resulting in increased endothelial Bcl-2. Diabetes was induced with streptozotocin, and mice were sacrificed at 2 months of study to measure superoxide generation, leukostasis, and immunohistochemistry, and at 7 months to assess retinal histopathology. Diabetes of 2 months duration caused a significant decrease in expression of Bcl-2 in retina, upregulation of Bax in whole retina and isolated retinal microvessels, and increased generation of retinal superoxide and leukostasis. Seven months of diabetes caused a significant increase in the number of degenerate (acellular) capillaries in diabetic animals. Furthermore, overexpression of Bcl-2 in the vascular endothelium inhibited the diabetes-induced degeneration of retinal capillaries and aberrant superoxide generation, but had no effect on Bax expression or leukostasis. Therefore, overexpression of Bcl-2 in endothelial cells inhibits the capillary degeneration that is characteristic of the early stages of diabetic retinopathy, and this effect seems likely to involve inhibition of oxidative stress.

Rat retinal ganglion cells upregulate the pro-apoptotic BH3-only protein Bim after optic nerve transection

Increased expression of Bim, a pro-apoptotic member of the Bcl-2 family, has been shown to be critical for neuronal apoptosis. To study the involvement of Bim in injury-induced cell death in retina, Bim expression was studied in normal rat retina and in retina after optic nerve transection using quantitative RT-PCR and immunohistochemistry. As a complement to this, the apoptotic regulators Bax, Bcl-2, caspase-3 and phosphorylated c-jun were studied. The relative levels of Bim mRNA in retina were significantly higher 4 days after optic nerve transection and below normal levels at 14 days after transection. A parallel increase in the number of Bim-immunoreactive cells in the retinal ganglion cell layer could be seen. Bim-immunoreactivity localized to retrogradely True Blue-labeled retinal ganglion cells. The relative mRNA levels for both Bax and Bcl-2 were higher at 4 days after transection when compared to normal. Immunoreactivity for Bax, Bcl-2 as well as for caspase-3 and phosphorylated c-jun, indicative of cell death, localized to True Blue-identified retinal ganglion cells 4 days after injury. Bcl-2 immunoreactivity was also seen on other cells, most likely Müller glia cells. In addition, optic nerve transection caused an increase in Bim, Bax, and Bcl-2 mRNA levels in optic nerve and superior colliculus. Our results suggest that Bim is involved in injury-induced retinal ganglion cell death and indicate that the increase in Bim and Bax expression promote cell death of axotomized retinal ganglion cells whereas the elevation in Bcl-2 in retina may contribute to the control of the extent of apoptosis after the optic nerve transection.