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Study Of The Effect Of VEGF Antisense Oligodeoxynucleotides On Eperimental Proliferative Retinopathy

Posted on:2003-02-11Degree:MasterType:Thesis
Country:ChinaCandidate:D Y DengFull Text:PDF
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[Background and Objective] Proliferative retinopathy is a series ofretinal diseases,including diabetic retinopathy,retinopathy of prematurity,central retinal vein occlussion and retinal periphlebitis,and so on,characterized as neovascularization,recurrent vitreous hemorrhage,proliferation and even traction retinal detachment and retinal atrophy. It causes the patient's serious vision damage even getting blind. Though not the optimal treatment,laser photocoagulation and vitrectomy are the only effective treatment for these diseases. Until now there is no effective drug to control the development of the conditions. The current studies showed that the VEGF played a key role in proliferative retinopathy,and the decrease of VEGF concentration maybe inhibit the neovascularization. In this study,a rat oxygen-induced retinopathy model,a model of proliferative retinopathy,is established to investigate the effect of VEGF and VEGF antisense oligodeoxynucleotides (ASODNs) on retinal neovascularization and the development of normal retinal vessels,as well as the influence of VEGF ASODNs on the concentration of VEGF in serum and in retina and vitreous fluids,so as to evaluate the therapeutic value of VEGF ASODNs in the proliferative retinopathy.[Methods] Sprague-Dawley(SD) rats 2 days after birth were randomized intofour groups and were designed as:Group 1 (normal control group) were breeding in room air. Group 2 (retrobulbar injection group),group 3 (caudal vein injection group) and group 4(non-disposal group) were exposed in hyperoxic enviroment for 10 days and then removed to room air. Animals of group 2 and group 3 were administrated VEGF ASODNs by retrobulbar injection and caudal vein injection respectively,but for group 1 and group 4 only saline at PH and PI?. The animals were killed painlessly at Pao to collect serum samples and the eyeballs were enucleated. For each animal,one eyeball was fixed by formaldehyde then cross-sectioned and stained with hematoxylin and eosin (HE). Through the cross-sections,the nuclei of proliferative retinal vessels were counted and the cross areas of retinal vessels were measured. Another eyeball was dissected to collect the retina and vitreous fluids samples (all tissues excluding cornea,sclera and lens). The levels of VEGF in the serum samples and in the retina and vitreous fluids samples were determined by competitive enzyme immunoassay.[Results] 1. The number of the nuclei of the new vessels in non-disposal groupwere 191.1 +15. 7,which was the highest among the four froups. The number in retrobulbar injection group (58. 7 +42. 0) and in caudal vein injection group (71.4+21.6) were both lower than that in non-disposal group (P < 0.01). Compared retrobulbar injection group with normal control group (37. 2+ 23. 5),there was no difference (P = 0.175). however,between caudal vein injection group and normal control group it was statistically different (P < 0.01). 2. The cross areas of retinal vessels of retrobulbar injection group (36601. 52 +9619. 78 m2) were the smallest,that of caudal vein injection group(46884.19 + 10908. 36 urn2),were higher than the former,but no difference(P = 0.55). The areas of normal control group (71603. 34+23753. 31 jam2) were statistically higher than the two groups administrated with VEGF ASODNs (P < 0.05). There was no statistical difference between normal and non-disposal (51164. 24+ 16285. 22 nm2)groups (P = 0. 064). The retinal vessels cross areas of non-disposal group were different to retrobulbar injection group (P < 0.05) and not different to caudal vein injection group (P = 0.55). There was no difference between the later two groups (P -0. 065). 3. The VEGF levels of retina and vitreous fluids in normal control group (35. 250 + 13. 738 ng/g) were significantly lower than that in caudal vein injection group (58. 678 +17. 958 ng/g) and that in non-disposal group(79. 919 +43. 043 ng/g ) (P < 0.05). It also was lower in retrobulbar injection group(38. 031 +13. 668 ng/g) than that in the above two groups(P < 0.05). However,there were no...
Keywords/Search Tags:proliferative retinopathy, antisense oligodeoxynucleotides, vascular endothelial growth factor, neovascularization, competitive enzyme immunoassay
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