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Background Primary open angle glaucoma(POAG) is a common type of glaucoma.It has been well known that a lot of factors are associated with the pathogenesis of POAG,but genetic factor plays a critical role.Optineurin (OPTN)gene is the second confirmed POAG-relevant gene,and screening its mutation in the population contribute to the deeply understanding of the pathogenesis of POAG.Objective The present study was to investigate the association between sequence variants of OPTN gene and POAG in Chinese patients.Methods DNA was isolated from peripheral blood of 100 POAG patients and 60 cataract individuals.The coding exons of OPTN gene were amplified by PCR.PCR products were then sequenced directly to assay the variants and contrasted to original sequence in GenBank.This study was approved by the Ethical Committee of Shenzhen Eye Hospital.All the subjects signed the written inform consent.Results A case-controlled study was designed.The mean intraocular pressure (IOP)of the POAG patients was (29.0±6.5)mmHg,and that of the cataract patients was (13.7 ±2.4)mmHg.Variant of synonymous coding T34T was found in 60 POAG patients.Genetic type frequencies of AA,GA and GG were 10％,50％ and 40％ in the POAG patients,and those of cataract patients were 0,25％ and 75％ respectively,showing significant difference between them (x2 =20.416,P =0.000).The allele frequencies of A and G were 35％ and 65％ in the POAG patients,and those of cataract patients were 12.5％ and 87.5％,with a statistically significant difference (x2 ＝ 19.464,P =0.000).The sequence changes of non-synonymous coding variants (M98K,691-692insA G,R545Q,H486R) were also found in both POAG and cataract patients,but no significant difference was seen in the genetype and allele frequencies between two groups (P＞0.05).Conclusions No obvious association of OPTN gene variant with POAG is verified.The variant of T34T maybe increase the risk of POAG.
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Background The main cause of filtering surgery failure is over proliferation of fibroblasts in filtering channels,leading to excessive fibrosis and scar formation.Researches determined that p38 mitogen-activated protein kinase(MAPK) signaling pathway plays an important role in fibroblast phenotype transition. Objective The present study was to investigate the inhibitory effect of p38 MAPK inhibitor on myofibroblasts transdifferentiation and the extracellular matrix synthesis after filtration surgery in rabbit eyes. Methods Trabeculectomy was performed on 24 eyes of 12 clean New Zealand white rabbits to establish the filtering operative models.The models were randomized into model group,SB203580 group and mitomycin C ( MMC ) group.1 ml SB203580 ( 0.2 g/L) was conjunctively injected at the end of operation in the rabbits of the SB203580 group,and the cotton piece with 0.2 g/L MMC solution was placed on the operative area for 3 minutes intraoperatively in the rabbits of the MMC group.The bleb appearances were examined under the slit lamp microscope,and intraocular pressure(IOP) was measured with Icare tonometer I,3,7,10,14 days after operation.0.2 ml aqueous humor was extracted and the conjunctive tissue at the filtering area was obtained 14 days after operation for the detection of α-smooth muscle actin (α-SMA) and fibronectin protein by ELISA.Expression of ACTA2 mRNA,connective tissue growth factor(CTGF) mRNA and alpha2 chain of type Ⅰ collagen( COL1A2 )mRNA in conjunctive tissue was assayed with fluorescence real-time PCR. Results Vascularization of fibrosis of filtering bleb were obvious in the eyes of the model group,and the bleb was flat and diffuse in the eyes of the SB203580 group and MMC group on 14 days following operation.No significant difference was seen in IOP before trabeculectomy among these three groups( F=0.065,P=0.937 ).IOP was gradually elevated with the increase of time after operation ( F =32.873,P =0.030 ).ELISA assay showed that α-SMA level in conjunctiva was lower in the SB203580 group and MMC group compared with the model group,and that of MMC group was significant lower than the SB203580 group( P＜0.05 ).Fibronectin level in conjunctiva was lower in the SB203580 group and MMC group compared with the model group,and that of MMC group was significant lower than the SB203580 group (P＜0.05).Fluorescence real-time PCR showed that expressions of the ACTA2 mRNA,CTGF mRNA and COL1A2 mRNA were significantly different among the three groups( P＜0.01 ),with the highest expression in model group and the lowest expression in the MMC group ( P ＜ 0.05 ). Conclusions Fibrotic reaction after trabeculectomy can be suppressed by inhibiting p38 MAPK signal pathway.The mechanism of SB203580 is to reduce the synthesis of myofibroblasts transdiffercntiation and extracellular matrix.
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BackgroundResearch demonstrated that vitamin D3 mediated by its receptor has the potent nonclassical effects,including immunomodulatory,antiinflammatory,and neuroprotective properties,and it can enhance the secretion and sensitivity of insulin and therefore down-regulate hyperglycemia and attenuate the corneal edema.ObjectiveThe present study was to investigate the protective effect of vitamin D3on ocular structure in experimental diabetic rat.Methods Twenty-two healthy SPF C57BL/6 rats were randomly divided into vitamine D3 group (8 rabbits),diabetic control group ( 11 rabbits) and normal control group ( 3 rabbits).2％ streptozotocin ( STZ,175 mg/kg)was intraperitoneally injected to create the diabetic models in the rats of the vitamine D3 group and diabetic control group.Blood glucose was examined for 3 times in the third day after STZ injection,and the rats with the blood glucose concentration ＞16.7 mmol/L was identified as the successful diabetic models.After modeling,the rat tail blood was collected for the monitoring of blood glucose.Two weeks after modeling,vitamine D3 was intraperitoneally injected in each week for 5 times.The fundus was examined using direct ophtalmoscope,and the eyeballs were obtained under the excessive anesthesia for the measurement of thickness of the central cornea,retina and choroids by histopathological examination once a week for 7 weeks after administration of vitamin D3.The administration of the animals complied with the Statement of ARVO.ResultsThe corneal edema appeared with the corneal thickness of (339.14± 11.13) μm in the first week and gradually attenuated with time elapse after modeling in the diabetic group ( F =382.446,P =0.000).The corneal thickness values were significantly decreased from the second week through the seventh week in the vitamin D3 group compared with diabetic control group(P＜0.05).The atrophy of the corneal epithelium was found from the fifth week to the seventh week in diabetic control group,but that in vitamin D3 group was slight (P＜0.05).The gradually thinning of the choroids was seen from the first week to the seventh week in the diabetic control group ( F =437.411,P =0.000 ),however,the thickness values in the vitamin D3 group were significantly increased in comparison with the diabetic control group in various time points (P＜0.05).The retina thickness was gradually reduced during the seven-week duration in the diabetic control group (F =91.859,P =0.000),but no significant change was identified in retina thickness in the vitamin D3 group(P＞0.05).ConclusionsVitamin D3 has prevent and therapeutic effects on experimental diabetic oculopathy.
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Background Scarring of the filtering bleb is a main cause of filtering surgical failure in glaucoma.It has been reposed that tetrandrine could suppress the proliferation of cultured human fibroblast of Tenons capsule in vitro and thus has the potential effect to prevent scarring after the filtering surgery. Objective Present study was to investigate the anti-cicatricial effect of tetrandrine drug delivery system(Tet DDS)during filtration surgery. Methods Filtration surgery was performed in bilateral eyes of 18 New Zealand white rabbits.The Tet DDS with 0.3 mg Tet,0.2 mg Tet or free-Tet were implanted subcunjunctially during the surgery.The filtering blebs were scored in 1 day,4,7,10,14 days after referring to the corneal thickness and bleb range under the slit-lamp biomicroscopy.The morphology of filtering bleb was assessed by in vivo confocal microscopy in 7 and 14 days after operation.The filtering bleb specimen was prepared in 7 and 14 days for the histopathological examination. Results The filtering bleb scores in Tet DDS implantation groups were significantly higher than those in free-Tet DDS group from 4 days through 14 days after trabeculectomy(P＜0.01),and the scores showed a considerably increase in 0.3 mg Tet DDS group compared with 0.2 mg Tet DDS group from 7 days through 14 days after trabeculectomy(P＜0.05).The filtering blebs of Tet DDS implantation groups were found with distinct subepithelial cystic spaces under the light microscopy and in vivo confocal microscopy on the 7th day and 14th day after surgery.Compared with free-Tet DDS group,the numbers of subepithelial mierocysts were much more(P＜0.01)and the area of microcysts was larger(P＜0.01)in Tet DDS group.The filtering tissue presented with more subepithelial microcysts and larger microcysts range in 0.3 mg Tet DDS group than 0.2 mg Tet DDS group in 7 and 14 days after operation(P＜0.05).The inflammatory cell infiltration wag milder in 0.3 mg Tet DDS group in comparison with 0.2 mg Tet DDS group and free-Ted DDS group.Conclusion Tet DDS has strong inhibitory effects on inflammatory cells activity and fibroblagt activity the early stage after filtering surgery and therefore improve the surgery success rate.