ABSTRACT
Clinician-scientists are doctors who perform laboratory-based or clinically oriented research and have direct patient contact.Not only do they play a critical role in the research and practice of translational medicine,but also they are the educators of the next generation of clinician-scientists.However,clinician-scientists are vanishing.It is urgent to train new clinician-scientists who can be engaged in clinic work,research,and also education.Thus,in order to correct understand the importance of the work of clinical scientists,from multi angle analysis of clinical scientists training problems that may be encountered in the process,the active improvement of the education system and condition,and sustained and efficient guidance to the outstanding seedlings are advocated.Besides,aspiring candidates are also encouraged to seek ideal guidance and support through their career,arrange their work reasonably,strengthen their cooperation and the management ability,and strive to grow into excellent clinician-scientists.
ABSTRACT
Background Matrix metalloproteinases (MMPs) play important roles in the formation of choroidal neovascularization (CNV),but its mail origin is not ocular cells in situ.Bone marrow-derived cells (BMCs) participate in the formation of CNV and is probably a primary source of expressing MMPs in CNV.MMP-2/MMP-13 is speculated to be the regulating target genes of miR188-5p.Objective This study was to verify whether BMCs are the main source of MMPs,and whether the MMP-2/MMP-13 expression is potentially regulated by miR188-5p.Methods BMCs expressed green fluorescent protein (GFP) from transgenic female C57BL/6J mice were transplanted to female wild-type C57BL/6J mice to establish C57BL/6J.GFP chimeras models,and 42 mice with chimerisms more than 85％ by flow cytometry were included as the experimental group.Other 42 wild-type C57BL/6J mice without the BMCs transplantation were enrolled as the control group.CNV was induced by laser coagulation of retinas on the mice of both groups.MMP-2/MMP-13 levels in the retinochoroid tissue were quantified by ELISA at day 1,3,5,7,10,14,and 28 after photocoagulation.The expression of miR188-5p mR NA in the retinochoroid tissue was assayed by real-time quantitative PCR (RT-qPCR).Immunofluorescence stain and fluorescent in situ hybridization were used to identify the MMP-2/MMP-13 and miR188-5p expressed by GFP-positive BMCs in CNV,and the expression level was quantified by images analysis.Results The proportion of GFP+ mouse mononuclear cells was (90.67±3.02) ％ in the C57BL/6J.GFP chimeras.The concentration changes of MMP-2/MMP-13 in retinochoroid homogenate showed a same tendency with the lapse of time between the experimental group and the control group (MMP-2:F=0.060,P =0.810 ; MMP-13:F =0.012,P =0.915).The expression level was zoomed in retinochoroid tissue after induce of CNV with the maximal value on the third day in both groups,and the proportion in the experimental group was 64.21％ ;while the expression level of MMP-13 was slowly raised after induce of CNV with the peak at the seventh day,and the proportion in the experimental group was 79.61％.A complementary association point of miR188-5p was exhibited in the 3 '-untranslated regions of MMP-2 or MMP-13 by target gene prediction.The expression level of miR188-5p mRNA in the BMCs of CNV area was sharply declined after induce of CNV with the lowest value on the seventh day.A negative correlation was found between the expressing level of miR188-5p and MMP-13 protein (r=-0.868,P＜0.05) as well as early stage of expression level of MMP-2 protein (r=-0.997,P＜ 0.05).Conclusions The elevation of MMP-2/MMP-13 expression levels is associated with the formation of CNV,and the regulation of miR188-5p expression in the BMCs of CNV area is responsible for increase of MMP-2/MMP-13 expression.The tendency of miR188-5p expression is inversed with MMP-2/MMP-13.
ABSTRACT
The introduction of anti-vascular endothelial growth factor (VEGF) therapy represents a landmark in the management of wet age-related macular degeneration (AMD).However,as a new therapy,several problems such as durability of the therapeutic effects,medication side effects,and medication selection have emerged.We should make appoint of improving the therapeutic effect and safety by realizing the limitation of the therapy,monitoring the clinical potential adverse reactions of anti-VEGF agents,and recommending individualized treatment.
ABSTRACT
Objective To investigate the role of bone marrow-derived cells (EMC) plays in choroidal neovascularization (CNV).Methods Green fluorescent protein (C-FP) chimeric mice were built by transplanting BMC from GFP transgenic mice to adult wild type C57BL/6J mice.Retinal laser photocoagulation was used to induce CNV in the chimeric mice (treated group) and adult wild type mice (control group).Four weeks later,choroidal flatmount was prepared to detect GFP positive BMC expression in the CNV lesions,and immunofluorescence stain was used to determine the expression of vascular endothelia growth factor (VEGF) and basic fibroblast cell growth factor (bFGF).Results Twenty-nine days after photocoagulation lots of GFP positive BMC presented in the CNV area,which accounted approximate 16.22% of the total CNV area.Some BMC in the CNV area expressed VEGF and bFGF.Conclusions BMC may play an important role in CNV by forming new vessles and secreting angiogenic factors.