血管内皮生长因子C的局部腺病毒递送诱导兔结膜淋巴管生成

IF 2 4区医学 Q2 OPHTHALMOLOGY

Ophthalmic Research Pub Date : 2023-01-01 Epub Date: 2023-08-09 DOI:10.1159/000533427

Dusan Rasic, Martin Wirenfeldt, Anne Louise Askou, Thomas J Corydon, Niklas Telinius

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引用次数: 0

摘要

本研究的目的是确定是否可以通过腺病毒传递VEGF-C诱导结膜淋巴管生成。方法17只新西兰白兔在结膜下注射含有3.5 × 10^7个斑块形成单位的腺病毒载体，该载体含有编码VEGF-C的基因(Ad-VEGF-C)。对照实验采用对侧眼(等量生理盐水或空载体)。两周后，用台盼蓝结膜淋巴管造影检查动物，采集眼睛进行组织学和免疫组化(podoplanin和CD31)。结果strypan蓝色结膜淋巴管造影显示，Ad-VEGF-C组结膜血管网络明显比对照组更广泛:血管长度/分析面积为1.35±0.67比0.28±0.17 (P=<0.0001)。免疫组织化学证实了这一发现，与对照组相比，淋巴血管数量显著增加，为34±9 / mm2，而13±8 / mm2 (P=0.0019)。淋巴横截面积显著增加;32500±7900µm2 / mm2 vs 17600±9700µm2 / mm2 (P=0.0149)。血管定量显示Ad-VEGF-C和对照组的血管密度无显著差异，分别为19±9 / mm2和14±8 / mm2 (P=0.1971)。两组总血管面积分别为13200±7600µm2 / mm2和7100±3000µm2 / mm2，差异无统计学意义(P=0.0715)。用腺病毒载体(VEGF-C或空载体)治疗的眼睛对载体产生反应性细胞反应，主要是淋巴细胞。讨论/结论本研究证明单次在结膜下注射Ad-VEGF-C诱导结膜淋巴管生成的可行性。未来的研究将探索如何将其用于治疗目的。

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Local Adenoviral Delivery of Vascular Endothelial Growth Factor C Induces Lymphangiogenesis in the Conjunctiva in Rabbits.

Introduction: The purpose of this study was to determine if conjunctival lymphangiogenesis can be induced using adenoviral delivery of vascular endothelial growth factor C (VEGF-C).

Methods: Seventeen New Zealand white rabbits received a subconjunctival injection containing 3.5 × 107 plaque-forming units of an adenoviral vector containing the gene-encoding VEGF-C (Ad-VEGF-C). The contralateral eye was used for control experiment (the same volume of either saline or an empty vector). After 2 weeks, the animals were examined with trypan blue conjunctival lymphangiography, and the eyes were harvested for histology and immunohistochemistry (podoplanin and CD31).

Results: Trypan blue conjunctival lymphangiography revealed significantly more extensive conjunctival vessel network in the Ad-VEGF-C group compared with control: 1.35 ± 0.67 versus 0.28 ± 0.17 vessel length/analysed area (p = <0.0001). This finding was confirmed with immunohistochemistry, where a significant increase in the number of lymphatic vessels was found compared to control; 34 ± 9 per mm2 versus 13 ± 8 per mm2 (p = 0.0019). Furthermore, there was a significant increase in lymphatic cross-sectional area; 32,500 ± 7,900 µm2 per mm2 versus 17,600 ± 9,700 µm2 per mm2 (p = 0.0149). Quantification of blood vessels revealed no significant difference in blood vessel density between Ad-VEGF-C and control; 19 ± 9 per mm2 versus 14 ± 8 per mm2 (p = 0.1971). There was no significant difference in total blood vessel area; 13,200 ± 7,600 µm2 per mm2 versus 7,100 ± 3,000 µm2 per mm2 (p = 0.0715). Eyes treated with an adenoviral vector (VEGF-C or empty vector) responded with a reactive cellular response, predominantly lymphocytes, towards the vector.

Conclusion: The study demonstrates the feasibility of inducing conjunctival lymphangiogenesis with a single subconjunctival injection of Ad-VEGF-C. Future studies will explore how this can be used with a therapeutic purpose.

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来源期刊

Ophthalmic Research 医学-眼科学

CiteScore

3.80

自引率

4.80%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Ophthalmic Research'' features original papers and reviews reporting on translational and clinical studies. Authors from throughout the world cover research topics on every field in connection with physical, physiologic, pharmacological, biochemical and molecular biological aspects of ophthalmology. This journal also aims to provide a record of international clinical research for both researchers and clinicians in ophthalmology. Finally, the transfer of information from fundamental research to clinical research and clinical practice is particularly welcome.