Bioinformatics analysis of potential essential genes that response to the high intraocular pressure on astrocyte due to glaucoma.

AIM: To study the gene expression response and predict the network in cell due to pressure effects on optic nerve injury of glaucoma. METHODS: We used glaucoma related microarray data in public database [Gene Expression Omnibus (GEO)] to explore the potential gene expression changes as well as correspondent biological process alterations due to increased pressure in astrocytes during glaucoma development. RESULTS: A total of six genes were identified to be related with pressure increasing. Through the annotation and network analysis, we found these genes might be involved in cell morphological remodeling, angiogenesis, mismatch repair. CONCLUSION: Increasing pressure in glaucoma on astrocytes might cause gene expression alterations, which might induce some cellular responses changes.

Resveratrol attenuates doxorubicin-induced cardiomyocyte apoptosis in lymphoma nude mice by heme oxygenase-1 induction.

Doxorubicin (DOX) has been used in a variety of human malignancies for decades, in particular of lymphoma. But increased cardiomyocyte apoptosis has been implicated in its cardiotoxicity. Resveratrol (RES) generates cardiovascular protective effects by heme oxygenase-1(HO-1)-mediated mechanism. The present study was designed to determine whether RES protected cardiomyocyte against apoptosis through induction of HO-1 in lymphoma nude mouse in vivo. After being developed into lymphoma model, 40 male Balb/c nude mice were randomized to one of the following four treatments (10 mice per group): control, DOX, DOX + RES and DOX + RES + HO-1 inhibitor (zinc protoporphyrin IX, ZnPP). The results showed that DOX injection markedly decreased the body weight, the heart weight and the ratio of heart weight to body weight, but inversely increased cardiomyocyte apoptosis and the level of serum lactate dehydrogenase and creatine kinase. Moreover, DOX injection attenuated HO-1 expression and enzymatic activity as well as increased P53 expression, modulated Bcl-2/Bax expression and enhanced caspase 3 activity. These cardiotoxic effects of DOX were ameliorated by its combination with RES. However, the protective effects of RES were reversed by the addition of ZnPP. Taken together, it is concluded that HO-1 plays a core role for protective action of RES in DOX-induced cardiomyocyte apoptosis in lymphoma nude mice.

Effect of erythropoietin on the expression of HIF-1 and iNOS in retina in chronic ocular hypertension rats.

AIM: To research the effect of erythropoietin (EPO) to the HIF-1\iNOS signal transduction path in retina in chronic ocular hypertension rat. METHODS: One hundred and twenty Wistar rats were divided into 12 groups randomly. Two episcleral veins were coagulated unilaterally in rats with electric coagulator to establish the glaucoma model. PT-PCR and Western Blot analysis were used to examine the expression of Caspase-9 genes in retina. And the changes of ERG-b wave before and after were detected using EPO. RESULTS: In EPO drug treatment group, the amplitude of ERG-b wave of retina restored remarkably. There was significant difference between two groups (P<0.05). The expressions of HIF-1\iNOS mRNA and protein in EPO drug treatment group were weakened remarkably. It was statistically different compared with the non-drug treatment group. CONCLUSION: One of protect mechanisms of EPO to injured retina caused by chronic intraocular hypertension is through HIF-1\iNOS signal conduct path.

IOP-lowering effects for the application of human umbilical vein in non-penetrating deep sclerostomy in rabbits.

AIM: To estimate the effects of human umbilical vein (HUV) implanted under the sclera of glaucoma model on intraocular pressure (IOP) lowering and to investigate its related mechanisms METHODS: A total of 20 human umbilical veins (HUV) were collected from healthy fetus umbilical core. After the establishment of glaucoma model in rabbits, human freeze-dried umbilical vein was implanted under the sclera during NPDS, while for control group, sclerostomy was performed without implant. The formation of the filtration bleb and IOP were detected every 24 hours before surgery and on day 3, 7, 10 and 14 after surgery. Handheld pen-type Tono-pen II tonometer was used to measure IOP after topical anesthesia treatment. Each measurement has three duplicates. The incision recovery, filtration, conjunctiva congestion and anterior chamber inflammation were observed everyday after surgery. RESULTS: IOP was decreased dramatically with less inflammation than traditional sclerostomies with the application of HUV. The significant differences of IOP between the NPDS with and without HUV implant groups were shown up from 10 days after surgery. The average IOP in NPDS without HUV implant was 14.25mmHg, while for NPDS with HUV implant group, it was 12.30mmHg. This structure of filtration bleb, which allowed the aqueous humor to leave the eye, was formed for any type of surgery. However, 1-2 weeks later, filtration bleb was still existed in the group of sclerostomy with HUV implant and more stable than that of the surgery without HUV implant. Histological observations were performed on day 3, 7 and 14 after surgery. For the eyes under sclerostomy with HUV implant, HUV lumina was shown up on 3 days after surgery with few fibroblast cells near the sclera. On 7 days after surgery, HUV lumina was stably maintained but with obvious fibroblast cells and inflammatory cell. On 14 days after surgery, HUV lumina was still clearly observed but with scarring formation, which suggests that the IOP lowering effects might result from an effective drainage structure formation. CONCLUSION: HUV might be an alternative material to make the drainage pathway for non-penetrating deep sclerostomy.

Effect of aminoguanidine on caspase-3 expression in rat retina after ischemia-reperfusion injury.

AIM: To investigate the effect of aminoguanidine (AG) on the expression of caspase-3 in rat retina after ischemia- reperfusion injury. METHODS: The rats were anesthetized with 30mg/kg sodium pentobarbital introperitoneal(ip) injections. After topical application of 10g/L dicaine, the anterior chamber was punctured with a 5-gauge needle connected to a bottle containing normal saline. Intraocular pressure was raised to 100 mmHg by elevating the saline container. The infusion needle was removed from the anterior chamber 60 minutes later. Reperfusion of the retinal vasculature was confirmed by fundus examination. AG 100mg/kg was ip injected in drug group. The rats were then euthanatized at 6, 24, and 72 hours after reperfusion, and their eyes were enucleated for immunohistochemistry. RESULTS: No specific staining was detected by using the caspase-3 antibody in the retina of control group. In ischemia group, the protein of caspase-3 was over-expressed at 6 hours and relieved at 24 hours and 72 hours, while with drug treatment, the expression of protein of caspase-3 was decreased at each time point. CONCLUSION: AG provides retinal protection against ischemia-reperfusion injury in rat retina, probably through an inducible NOS-dependent mechanism.