Objective
To review the research progress of growth factor sustained-release microspheres in fat transplantation.
Methods
The recently published 1iterature at home and abroad related the growth factor sustained-release microspheres in fat transplantation was reviewed and analyzed.
Results
The sustained-release microsphere carrier materials include natural polymer materials and synthetic polymer materials.The sustained-release complexes of different microsphere materials with different growth factors can promote the vascularization of transplanted fat in a timely manner, improve the survival rate of grafts, and reduce the incidence of complications such as liquefaction, calcification, and necrosis.
Conclusion
The growth factor sustained-release microspheres have the characteristics of persistence and controllability, which is a research hotspot in the field of fat transplantation and has broad application prospects.
Choroidal neovascularization is the leading causes of central vision loss in wet age-related macular degeneration (wAMD) patients. Smoking not only aggravates the incidence and severity of the choroidal neovascularization of wAMD, but also affects the clinical treatment, making the prognosis worse. Nicotine, as an important harmful substance in tobacco, is an easily addictive and highly toxic alkaloid. Animal experiments and clinical studies have confirmed that nicotine can aggravate wAMD by mediating angiogenesis through nicotinic acetylcholine receptor, bone marrow blasts, inflammation, complement system, etc. Therefore, in order to early take appropriate intervention measures to prevent and delay the development, we should actively explore the exact pathogenesis by which nicotine aggravates the choroidal neovascularization.
Objective To investigate the effects of recombinant adeno-associated virus type-2 (rAAV2) mediated delivery of pigment epitheliumderived factor (PEDF) on oxygen-induced retinal neovascularization (OIRNV) in mice. Methods A total of 22 C57/BL6 mice at the age of 3 days received intravitreal injections of 1 mu;l rAAV2-PEDF and rAAV2EGFP into the left eyes (experimental group) and the right eyes (control group). All mice were put into the oxygen box right after the injection to induce the OIRNV model.4 mice were sacrificed and PEDF protein in retina was measured by western blot at postnatal days 13 (P13). Twelve mice underwent retinal angiography with high molecular weight fluoresceindextran, and another 6 mice were sacrificed for retinal lectin immunohistochemistry staining at P17. Absolute and relative nonperfusion areas of retinal neovascularization were analyzed by Image-Pro Plus 5.1 software. Results The expression level of PEDF protein was higher in the experimental group than that in the control group.The absolute nonperfusion area was (0.96plusmn;0.22) mm2 in the experimental group and (1.96plusmn;0.34) mm2 in the control group; the difference between the two groups was significant（t=-8.554, P＜0.01）. The relative nonperfusion area was (8.64plusmn;1.52)% in the experimental group and (17.27plusmn;2.98)% in the control group with a significant difference between the two groups (t=-8.97, P＜0.01).The absolute area of retinal neovascularization was (0.37plusmn;0.11) mm2 in the experimental group which was obviously higher than (1.26plusmn;0.38) mm2 in the control group (t=-7.8, P＜0.01); the relative areas in experimental and control groups was (3.96plusmn;0.66)% and (11.45plusmn;2.06)%, respectively, whose difference is apparently(t=-8.51, P＜0.01).The areas of retina neovascularization were (0.11plusmn;0.003) mm2 and (0.41plusmn;0.02) mm2 in the experimental and control groups, respectively, and the difference between the two groups was significant（t=-5.14, P＜0.01）.Conclusions PEDF protein can stably express in the mice retina after rAAV2-PEDF transfetion. rAAV2-PEDF can decrease the retinal non-perfusion areas and inhibit the retinal neovascularization in OIRNV mice.
Objective
To determine the effect of methimazole (MMI) on retinal vascular development in neonatal rats, and to investigate the relationship between the concentration of insulin-like growth factor-I (IGF-I) in serum and the development of normal blood vessels and between the concentration of IGF-I and the formation of abnormal blood vessels.
Methods
There were 75 neonatal SpragueDawley rats in experimental group whose mothers were raised with water with 0.1% MMI at the first day of parturition. Another 50 neonatal rats were in the control group whose mothers were raised with normal water. The rats in the two groups were sub-divided into 4day and 10day subgroup, respectively. The retinal flatmount of the right eyes were stained with adenosine diphosphatase (ADPase); with the paraffin section of the left eyes, the number of nucleolus breaking through retinal inner limiting membrane was counted and the retinal blood vessels were evaluated. Serum IGF-I levels were detected by radioimmunoassay, and the weight of the neonatal rats in each group were observed and recorded.
Results
The incidence of retinal neovascularization in 10 day MMI group was 27%, and 0% in 4-day MMI group and control group. The serum IGF-I level in 4-day and 10-day MMI group (73.07 ng/ml, 175.13 ng/ml) was obviously lower than which in the 4-day and 10-day control group (168.73 ng/ml,306.38 ng/ml) （P=0.00）. Obvious slow growth of the neonatal rats was found in MMI group compared with which in the control group.
Conculsions
MMI may inhibit the normal growth of retinal blood vessels and lead neovascularization, which may relate to the initial decrease of the serum IGF-I level.
(Chin J Ocul Fundus Dis, 2007, 23: 198-201)
PURPOSE:To observe the clinical features of the macular hemorrhage in myopes.
METHOD:Twenty-four patients(30 eyes)with myopic macular hemorrhage were examined with slitlamp biomicroscopy,funduscope,A/B ultrasonography,and fundus fluorecein angiography(FFA). The patients were followed up for 3~18 months(average 12 months). RESULTS: Four of 26 eyes with
macular hemorrhage examined with FFA were found to be due to choroidal neovaseulature,and they were associated with posterior staphyloma. The other 22 eyes without neovascular change were thought to be simple type,and 19 of them were associated with lacquer cracks. The hemorrhage in simple type cases deminished usually within 1~3 months.
CONCLUSION:Myopic macular hemorrhagic eyes of neovascular type resulted usually in recurrent hemorrhage and worse prognosis in visual acuity than
those of simple type.
（Chin J Ocul Fundus Dis,1996,12: 220-222）
ObjectiveTo study the inhibitory effects of pigment epithelium derived factor (PEDF) on oxygen-induced retinal neovascularization in mice, and to investigate the possible involvement of interleukin-1β (IL-1β) in the neovascular-inhibitory function of PEDF.
Methods A total of 140 postnatal day (P)7 C57BL/6 mice were randomly divided into normal control group, oxygen-induced retinopathy (OIR) model group, PEDF treatment group and PBS treatment control group. All mice except normal control group with their mothers were exposed to (75±2)% oxygen environment for 5 days and then kept in room air for another 5 days to establish the OIR model. Mice in normal control group were kept in room air only. At P12 and P14, respectively, mice in PEDF treatment group received intravitreous injections of 1 μl PEDF (2 μg/μl), while PBS treatment control group received the same volume of PBS (10 mmol/L, pH7.4).All mice were euthanized at P17 and eyes were isolated. The changes of retinal vessels were observed on retinal flat mounts and cryosections by fluorescence microscopy. Retinal specimens were prepared for IL-1β protein and mRNA analysis by Western blot and real time fluorescence quantitative reverse transcription-polymerase chain reaction (Real-time RT-PCR).
ResultsChanges of retinal vessels had been viewed by fluorescence microscopy on flat-mounted retina, the relative retinal neovascularization areas were significantly increased in OIR model group compared with normal control group (t=15.02, P < 0.01), and the relative retinal neovascularization areas were obviously smaller in PEDF treatment group than those in PBS treatment control group (t=5.96, P < 0.01). Fluorescence staining revealed that retinal vascular tufts were extending from outer plexiform layer (OPL) to ganglion cell layer (GCL) of the retina along with multiple interconnections; Neovascular tufts in OIR model group and PBS treatment control group were presenting distinctly more than those of normal control group and PEDF treatment group. The specific expression levels of IL-1β protein in retinas of OIR mice by Western-blot analysis were higher than those of normal control group(t=3.35, P < 0.05), While these of PEDF treatment group showed a considerable decline in comparison with PBS treatment control group (P < 0.01), and there were no difference in normal control group and PEDF-treated group (F=11.764, P > 0.05). Similarly, expression levels of IL-1β mRNA tested by Real-time RT-PCR were obviously increased in the OIR model group when compared to normal control group(t=4.43, P < 0.01). After treated with PEDF, expression levels of IL-1β mRNA showed a considerable decrease when compared to PBS treatment control group (P < 0.01), and there were no difference in normal control group and PEDF-treated group (F=11.15, P > 0.05).
ConclusionsPEDF can inhibit oxygen-induced retinal neovascularization. The mechanism may be related to that PEDF can downregulate the expression of IL-1β in retina.
Interleukin-18 is an inactive precursor which lacks a signal peptide, it has a role in regulating retinal pathological angiogenesis. It also inhibits experimental choroidal neovascularization (CNV) via interferon-γand thrombospondin-1. Currently little is known about its mechanisms of inhibition for CNV, may be speculated to be due to effects of anti-angiogenesis, down-regulates vascular permeability and lower vascular endothelial growth factor (VEGF) levels via directly acting on the vascular endothelial cell and epithelial cells. Exogenous administration of mature recombinant interleukin-18 has no adverse effect on retinal pigment epithelial cell viability. In addition, the anti-VEGF role of interleukin-18 is tested to be safe and effective for humans. Interleukin-18 alone or in combination with anti-VEGF shows to be a good prospect for improving the prognosis of experimental CNV. However, more large clinical studies are required to confirm the exact efficacy of interleukin-18 for CNV.
Objective To observe the revascularization process of chemically extracted acellular allogeneous nerve graft in repairing rat sciatic nerve defect. Methods Eighty adult male SD rats were selected. The sciatic nerve trunks from ischial tuberosity to the ramus of tibiofibular nerve of 16 SD rats were obtained and were prepared into acellular nerve stents by chemical reagent. Sixty-four SD rats were used to prepare the models of sciatic nerve defect (1.0 cm) and thereafter were randomized into two groups (n=32): experimental group in which acellular allogeneous nerve grafts were adopted and control group in which orthotopic transplantation of autologous nerve grafts were adopted. Postoperatively, the general conditions of all rats were observed, and the gross and ALP staining observation were conducted at 5, 7, 10, 14, 21, 28 days and 2, 3 months, respectively. Results All the incisions were healed by first intention. Trail ing status and toe’s dysfunction in extension happened to the right hindl imb of rats in two groups and were improved 6 weeks after operation. General observation showed that the grafts of two groups connected well to the nerves, with appearances similar to that of normal nerve. ALP staining demonstrated that the experimental group had no ingrowth of microvessel but the control group had ingrowth of microvessel 5 days after operation; the experimental group had ingrowth of microvessel but both groups had no microvessel 7 days after operation; few longitudinal microvessel throughout the grafts were observed in both groups 10, 14 and 21 days after operation; no obvious difference in capillary network of grafts was observed between two groups 28 days after operation; and the microvascular architecture of grafts in both groups were similar to that of normal nerve 2 and 3 months after operation. Conclusion When the chemically extracted allogeneous nerve graft is adopted to repair the peripheral nerve defect, new blood microvessels can grow into grafts timely and effectively.
Objective
To observe the OCT angiography imaging features of choroidal neovascularization (CNV) with different activity in age-related macular degeneration (AMD).
Methods
A retrospective case analysis. Forty-two eyes of 33 patients (21 males and 12 females, aged 65.3±8.61 years) who were diagnosed with AMD by multi-mode fundus imaging examination at the Ophthalmology Department of Yunnan Second People's Hospital during January 2017 and October 2018 were enrolled in this study. All patients underwent BCVA, slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus colorized photography, FAF, FFA and OCT examinations. The patients were divided into active CNV (27 eyes of 19 patients) and inactive CNV (15 eyes of 14 patients) by comprehensive analysis of fundus imaging characteristics and treatment process. The imaging features of OCTA in the two groups were compared. The number of eyes of each active or inactive indicator in the active CNV group and the inactive CNV group was calculated, and the composition ratio of each group of the indicators was subjected to the χ2 test.
Results
Among the 27 eyes of active CNV, 22 eyes (81.5%) of OCTA showed abundant small capillary branching structure, while 13 eyes (13.3%) of 15 eyes of inactive CNV showed more coarse blood vessel. Among the 27 eyes of active CNV, 26 eyes (96.3%) of OCTA showed that the marginal vascular end points of CNV lesions were "arcaded" or "ring", while 12 eyes (80.0%) of 15 eyes of inactive CNV showed the presence of isolated branches of peripheral vessels. Among the 27 eyes with active CNV lesions, there were no large feeder vessels inside the lesions, and 8 (53.3%) of the 15 inactive CNV lesions showed feeder vessels in the center of the lesion. Among the 27 eyes with active lesions, 23 eyes (85.2%) of OCTA showed a low-reflection "halo" around the CNV lesion, and no low-reflection "halo" structure was observed in the 5 eyes of the inactive CNV lesion. The statistical results showed that there were abundant small blood vessel branches (χ2=22.759, P=0.000), annular anastomosis around the lesion (χ2=31.704, P=0.000), low-reflection halo (χ2=32.327, P=0.000), and large nourishing blood vessels (χ2=26.063, P=0.000), dilated choroidal vessels (χ2=32.912, P=0.000). All the above indicators were statistically different between the two groups.
Conclusion
The abundant small vessel branches in OCTA, the surrounding anastomosis in a ring structure and the low reflex halo around the lesion are markers of active CNV, while the large feeding vessels and dilated choroidal vessels are indicators of inactive CNV.
Objective To observe the inhibitory effects of gene transfer of canstatin on retinal neovascularization in mice. Methods Fifty-six 7-day-old C57BL/6J mice were randomly divided into control group,oxygen-induced retinopathy (OIR) group, empty vector group and treated group,14 mices in each group. Except for the control group,the mice in the other groups were exposed to (75plusmn;2)% oxygen for 5 days and then back to the normal air to establish the model of OIR. On postnatal 12 day, the treated group was received intravitreal injection of canstatin pCMV-HA, while the empty vector group was received the same volume of empty plasmid.The changes of retinal vessels were observed by Evans blue angiography on postnatal 17 day. With parafin section which stained by hematoxylin and eosin, then the number of endotheliocyte nuclei breaking throuhgh the internal limiting membrane（ILM） was observed and counted by optical microscope.Results Retinal blood vessels distributed regularly in treated group compared with OIR group and empty vector group.The differences of the number of endotheliocyte nuclei breaking throuhgh ILM in treated group was significant compared with the other two groups（F=39.006，Plt;0.001).Conclusion The canstatin pCMV-HA can effectively inhibit the retinalneovascularization in OIR.
