Mesh : Animals Rabbits Fluorouracil / therapeutic use pharmacology Glaucoma / surgery physiopathology drug therapy Vascular Endothelial Growth Factor C / metabolism Trabeculectomy / methods Disease Models, Animal Intraocular Pressure / physiology Antimetabolites / pharmacology therapeutic use Tomography, Optical Coherence Conjunctiva RNA, Messenger / genetics

来  源:   DOI:10.1167/iovs.65.5.32   PDF(Pubmed)

Abstract:
UNASSIGNED: To evaluate VEGF-C-induced lymphoproliferation in conjunction with 5-fluorouracil (5-FU) antimetabolite treatment in a rabbit glaucoma filtration surgery (GFS) model.
UNASSIGNED: Thirty-two rabbits underwent GFS and were assigned to four groups (n = 8 each) defined by subconjunctival drug treatment: (a) VEGF-C combined with 5-FU, (b) 5-FU, (c) VEGF-C, (d) and control. Bleb survival, bleb measurements, and IOP were evaluated over 30 days. At the end, histology and anterior segment OCT were performed on some eyes. mRNA was isolated from the remaining eyes for RT-PCR evaluation of vessel-specific markers (lymphatics, podoplanin and LYVE-1; and blood vessels, CD31).
UNASSIGNED: Qualitatively and quantitatively, VEGF-C combined with 5-FU resulted in blebs which were posteriorly longer and wider than the other conditions: vs. 5-FU (P = 0.043 for longer, P = 0.046 for wider), vs. VEGF-C (P < 0.001, P < 0.001) and vs. control (P < 0.001, P < 0.001). After 30 days, the VEGF-C combined with 5-FU condition resulted in longer bleb survival compared with 5-FU (P = 0.025), VEGF-C (P < 0.001), and control (P < 0.001). Only the VEGF-C combined with 5-FU condition showed a negative correlation between IOP and time that was statistically significant (r = -0.533; P = 0.034). Anterior segment OCT and histology demonstrated larger blebs for the VEGF-C combined with 5-FU condition. Only conditions including VEGF-C led to increased expression of lymphatic markers (LYVE-1, P < 0.001-0.008 and podoplanin, P = 0.002-0.011). Expression of CD31 was not different between the groups (P = 0.978).
UNASSIGNED: Adding VEGF-C lymphoproliferation to standard antimetabolite treatment improved rabbit GFS success and may suggest a future strategy to improve human GFSs.
摘要:
在兔青光眼滤过手术(GFS)模型中评估VEGF-C诱导的淋巴增殖与5-氟尿嘧啶(5-FU)抗代谢物治疗的结合。
32只兔子接受了GFS,并分为四组(每组n=8),通过结膜下药物治疗定义:(a)VEGF-C联合5-FU,(b)5-FU,(c)VEGF-C,(d)和控制。Bleb生存,气泡测量,和IOP在30天内进行评估。最后,对一些眼睛进行组织学和眼前节OCT检查。从剩余的眼睛中分离mRNA,用于RT-PCR评估血管特异性标志物(淋巴管,podoplanin和LYVE-1;和血管,CD31)。
定性和定量,VEGF-C与5-FU组合导致的气泡比其他条件后长和宽:5-FU(较长时P=0.043,P=0.046对于较宽),vs.VEGF-C(P<0.001,P<0.001)与对照组(P<0.001,P<0.001)。30天后,与5-FU相比,VEGF-C联合5-FU条件导致更长的气泡生存期(P=0.025),VEGF-C(P<0.001),和对照组(P<0.001)。只有VEGF-C合并5-FU的患者眼压与时间呈负相关,差异有统计学意义(r=-0.533;P=0.034)。前节OCT和组织学显示,VEGF-C合并5-FU的情况下有较大的气泡。仅包括VEGF-C在内的条件导致淋巴标记物表达增加(LYVE-1,P<0.001-0.008和podoplanin,P=0.002-0.011)。CD31的表达在各组之间没有差异(P=0.978)。
在标准抗代谢物治疗中添加VEGF-C淋巴增殖可提高兔GFS的成功率,并可能提出改善人类GFS的未来策略。
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