Objective：To observe the protective effect of ginkgo bilo ba extrac t (EGb 761), a free radical scavenger, on the photoreceptor cells after lighti nduced retinal damage. Methods：Seventytwo female SpragueDa wley (SD) rats we re randomly divided into 4 groups: normal control group, lightinduced retinal da m age model group, model+physiological saline group, and model+EGb 761 group, with 18 rats in each group. All of the rats except the ones in the control group were exposed to white light at (2740plusmn;120) lx for 6 hours after the dark adap tation for 24 hours to set up the lightinduced retinal damage model. Rats in m o del + physiological saline group and model+EGb 761 group were intraperitoneall y injected daily with physiological saline and 0.35% EGb 761 (100 mg/kg), respec tively 7 days before and 14 days after the light exposure. Apoptosis of photorec eptor cells was detected 4 days after light exposure; 7 and 14 days after light exposure, histopathological examination was performed and the layer number of ou ter nuclear layers (ONL) on the superior and inferior retina was counted. Results：Four days after light exposure, the apoptosis of photorecep tor cells was fou nd on ONL in model, model+ physiological saline and model+EGb 761 group, and w as obviously less in model + EGb 761 group than in model and model+physiologic al saline group. Seven days after light exposure, the layers of ONL on the super ior retina were 3 to 4 in model and model+physiological saline group, and 7 to 8 in model+EGb 761 group; the mean of the layer number of ONL in model+EGb 761 group (6.92plusmn;0.82) was less than that in normal control group (8.40plusmn;0.95) (t=-1.416, P＜0.05), but significantly more than that in model (5.96 plusmn;1.36 ) and model+physiological saline group (5.90plusmn;1.40）（t=1.024, 1.084; P＜0.05). Fourteen days after light exposure, the layers of ONL on the superior retina were 0 to 1 in model and model+physiological saline group, and 3 to 4 i n model+EGb 761 group. The mean of the layer number of ONL in model+EGb 761 group (5.5 2plusmn;1.06) was significantly more than that in model (3.44plusmn;2.15) and model + physiological saline group (3.37plusmn;1.91) (t=2.082, 2.146, P＜0.05). Conclusion：EGb 761 can partially inhibit the apoptosis of pho toreceptor cells, thus exert protective effect on photoreceptor cells.
OBJECTIVE:To verify the safe dose of cephradine in intravitreal injection. METHODS:After injecting different doses of cephradine(100mu;g,200mu;g,250mu;g,300mu;g,400mu;g)into vitreous cavity of different group of rabbits the activities of the retinal enzymes (SDH,LDH )on different time (Id,3d, 7d ) were determined respectively, and the histological and ultrastructural changes of retinas were also observed simuhaneously. RESULTS:The activity of rellnal SDH and LDH was found to be decreased gradually with tbe icreasing of the dosage of intravitreal cephradine. The activities of SDH and LDH were found in the lowest level on tile 3rd and lsl day,but they recover to normal levels on tile 7th day after intravitreal in}eetion in 100mu;g,200mu;g groups,and still lower tban normal in the other groups. Histologically,retinal edema was found both in 100mu;g and 200mu;g groups,but degradation of retinal cells,and loss of cones and rods were round in the 250mu;g, 300mu;g and 400mu;g groups. CONCLUSION: The safe dose of intravitreal injection of cepbradlnc is 200mu;g. （Chin J Ocul Fundus Dis,1997,13:139-142 ）
ObjectiveTo evaluate the efficacy and security of intravitreous injection with triamcinolone acetonide (TA) for macular edema.MethodsA total of 41 eyes in 37 patients with macular edema who measured up were collected, including 21 eyes of 21 cases in retinal vein occlusion (RVO) group, 17 eyes of 13 cases in diabetic retinopathy (DR) group, and 3 eyes of 3 cases in the other-causes group. Before the treatment, the average visual acuity was 0.07, 0.06, and 0.08 in the 3 groups respectively, and the mean thickness of macular fovea detected by optic coherence tomography (OCT) was (974±394) and (873±213) in RVO and DR group, respectively. Intravitreous injection with 0.1 ml TA (40 mg/ml) was performed on each patient. The average follow-up duration was 8 months after the treatment. The visual acuity, intraocular pressure (IOP), changes of lens and ocular fundus, and retinal thichness at macular area before and after the treatment was observed and compared.ResultsAll eyes except one had improved visual acuity. The mean visual acuity improved to 0.25, 0.20, and 0.35 in the 3 groups respectively 6 months after the treatment. Alleviated or reducing macular edema was found in all of the patients. The average retinal thickness at macular fovea was (173±41) and (204±76) in RVO and DR group respectively 1 month after the treatment, which had statistical significance compared with that before the treatment (t =8.323, 6.842; P＜0.01). The intraocular pressure was ＞21 mm Hg (1 mm Hg = 0.133 kPa) in 6 eyes (14.6%), which mostly happened 1 week to 2 months after the injection, and was controlled to normal level after partially treated with βreceptor retarder. The cataract developed in 1 eye, and another patient with macular edema after vitrectomy due to diabetes had macular hole 2 months after the injection. There were 2 eyes underwent intravitreous injection with 0.1 ml TA 4-5 months after the first treatment due to the recurrence of macular edema in RVO and DR group respectively.ConclusionsIntravitreous injection with TA is a promising therapeutic method for macular edema that fails to respond to conventional treatment. Transient elevation of ocular pressure is the most common side effect. Further study is needed to assess the long-term efficacy and safety. (Chin J Ocul Fundus Dis, 2005,21:209-212)
Objective To investigate the dose-dependent relationship of bone marrow mesenchymal stem cells(MSCs) transplantation in improving ischemic myocardial dysfunction? in a rat ischemic heart model. Methods Myocardial infarction was induced in 32 inbred F344 rats by acute ligation of the left anterior descending(LAD) coronary artery. One week after ligation, the ratswere randomized? into four equal groups, with eight rats in each group. Equal volume Iscove’s modified Dulbecco’s medium was injected in the control group, 1×103(group 1), 1×105(group 2), and 1×107(group 3) 5-bromodeoxyuridine (BrdU) labeled bone marrow MSCs were injected into the infarcted myocardium. Cardiac function was evaluated by ultrasound before the ligation of the LAD, before the transplantation and the 4th week after transplantation. The expressions of BrdU,Connexin43,Myosin heavy chain β(MHC), and smooth muscle actin α(α-SMA) were detected by immunofluorescence and immunohistochemistry at the 4th week after transplantation. The amount of functional vessels stained by α-SMA was counted simultaneously. Results At the 4th week? after transplantation, the ejection fraction(EF) in goup 2 was more significantly improved than that in group1(0.54±0.20 vs. 0.34±0.16, P＝0.004) and EF in group 3 was more significantly improved than that in group 2(0.71±0.24 vs. 0.54±0.20,P＝0.018), whereas no significant difference between group 1 and control group was detected (0.34±0.16 vs. 0.36±0.15,Pgt;0.05). The BrdU labeled MSCs could be found in host myocardium. The number of cells in group 2 by double staining both for BrdU and for MHC observed in ischemic myocardium were significantly more than that in group 1? (323.20±91.62 n/HP vs. 51.75±27.58 n/HP,P＝0.049) and the same was true between group 3 and group 2(409.75±106.65 n/HP vs. 323.20±91.62 n/HP,Plt;0.001), whereas the result of control group was negative.The majority of transplanted cells were found positive staining both for MHC and for Connexin43 in all groups. There were lots of positive staining of α-SMA whose form were partly irregular in ischemic myocardium indicating that there was neovascularization in group1 and control group. More neovascularization in group2 was found than that in group 1 (28.38±12.79 n/HP vs. 22.75±9.07 n/HP, P＝0015) and more neovascularization in group 3 was found? than that in group 2 (35.63±13.27 n/HP vs. 28.38±12.79 n/HP, P＝0.002) . Conclusion Transplanted into infarcted myocardium, bone marrow MSCs may have significant and dose-dependent potential for cardiomyogenesis with functional recovery from myocardial ischemia.
Objective To evaluate the safety repeated intravitreal injection of bevacizumab (Avastin) with different dosage in rabbitsprime;eyes. Methods Fourteen chinchilla rabbits were randomly divided into 3 groups, including both eyes of 2 rabbits in the control group,the right eyes of the other 12 rabbits in the experimental group,and the left eyes of the 12 rabbits in the experimental control group. The eyes in the experimental group underwent intravitreal injection of bevacizumab with the dosage of 2.5 mg/0.1 ml and 5.0 mg/0.2 ml of bevacizumab; the eyes in the experimental control group underwent intravitreal injection of normal saline with the same dosage as in the experimental group. Injections were performed every two weeks and lasted six weeks. Clinical observation and retinal function tests were performed before and two days after every injection. The eyes were sacrificed 1 week and 4 weeks after last intravitreal injection respectively.Electron and optical microscope and TUNEL were performed.Results After intravitreal injection,no obvious anterior chamber flare, abnormal change of the ocular fundus, or vitreous opacity and hemorrhage was observed in all of the eyes.No change was found by indirect ophthalmoscope,Bultrasonic inspection, ultrasound biomicroscopy and optical coherence tomography. The number of anterior chamber flare before and after the injection with the dosage of 2.5 and 5.0 mg, the difference among the 3 groups didnprime;t differ much from each other (Pgt;0.05).Amplitude and pattern of ERG responses and flash VEP were similar between the control and experimental groups (Pgt;0.05). Some inflammatory cells were found in the some bevacizumabinjected eyes 1 week after injection, and vanished 3 weeks later. The histological configuration of the retina didnprime;t change in both experimental control and the control group. Electron microscopy showed that plasma cells were presented and vacuolelike change was observed in part of the photoreceptor cells in 5.0 mg experimental group 1 week after injections.Cellular apoptosis was observed in the photoreceptor cell layer. The number of apoptotic cells was more in 5.0 mg experimental group than that in the control and experimental control group 1 week after injections (Plt;0.01). Conclusion Multiintravitreal injection with 5.0 mg bevacizumab may have mild toxicity to the retina in the rabbits.
ObjectiveTo evaluate the security of intravitreal injection with ciproflaxacin to retina.MethodsTweenty-four rabbits were randomly divided into 4 groups with 6 rabbits in each group. 0.1 ml ciproflaxacin in doses of 2 500,5 000,and 10 000 μg was intravitreally injected into the rabbits eyes, retrospectively. And 0.1 ml saline solution was injected into the vitreous body of the rats in the control group. Indirect microscope, light microscope and electroretinogram (ERG) were used to observe the changes of ocular fundus.ResultsNormal results of light microscopy and ultrastructure were found in 250 μg and 500 μg groups; irregularly arranged outer and inner nuclear layers, dropsical or even lost ganglion cells, and ultrastructural changes were in 1 000 μg group. There was no apparent difference of ERG′s a and b amplitudes before and after intravitreal injection with ciproflaxacin in each group.ConclusionIntravitreal injection with ciproflaxacin is safe, and 500 μg or less is the secure dosage in rabbits' eyes. (Chin J Ocul Fundus Dis, 2005,21:180-182)
PURPOSE: To investigate the treatment of severe bacterial endophthalmitis. METHODS:The curative effects of vitrectomy after intravitreal antibiotics and steroids (IVAS)for the treatment of 23 patients with bacterial endophthalmitis (group I)and vitrectomy and IVA at the same time for the treatment of 28 patients with bacterial endopbthalmitis (group I)were analyzed retrospectively. RESULTS: The rate of curative effects of two groups were similar,while the marked curative effects in group I (47.8% )was significantly higher than that of the group I (17.9%). The average period of eliminating infiamation of group I was longer than that of group I , and the incidence of postoperative retinal detachment of group Ⅱ was 3 times more than that of group I . CONCLUSION :It was indicated that vitrectomy after IVAS may increase the security of vitrectomy and the curative effects of severe bacterial ndophthalmitis.
What drug dosage range is appropriate for treatment? What drug dosage range can maximally reduce the incidence of adverse drug reaction (ADR)? The gold zone method as a new method of evidence-based medical research was proposed to study those two blind areas of drug dosage in this article. Studying the dose-effect relationship, taking gold zone as the middle range and dividing empirical range into 3 sections were the key to study design. The evidence-based survey with extremely large sample showed a U-shaped rule existing between the antibiotics’ dosage and the incidence of ADR; and the dosage in gold zone appeared at the bottom of U-shaped curve. The gold zone method for determining dosage is a special breakthrough currently for solving those two blind areas of drug dosage
Objective To observe the influence of interleukin-1beta; (IL-1beta;) on the expression of phosphorylated signal transducers and activators of transcription 3 (pSTAT 3) in rat retinal Muuml;ller cells.Methods For in vitro study cultured Muuml;ller cells were treated with IL-1beta; of different concentrations (0, 0.1, 1, 5 and 10 ng/ml) for 24 hours. For in vivo study, 32 Sprague-Dawley（SD）rats were divided into 4 groups randomly (control group，100，500 and 1000 ng/ml group) with 8 rats in each group. After 24 hours of injection with phosphate buffered solution (PBS), or 100,500,1000 ng/ml IL-1beta; into the vitreous cavities of the above rats, retinas were harvested. The expressions of pSTAT3 in cultured Muuml;ller cells or treated retinas were evaluated by indirect immunofluorescence and western blotting.Results After 24 hours of incubation without IL-1beta;, pSTAT3 has little expression in cultured Muuml;ller cells, but was upregulated by 1 ng/ml or higher IL-1beta; in a dosagedependent manner (F=46.64, 43.78;P＜0.01). pSTAT3 was not expressed in adult rat retina, but was upregulated by vitreous injection of 100 ng/ml or higher IL-1beta; in a dosagedependent manner (F=73.53,43.70;P＜0.01).pSTAT3 expressed mainly in inner nuclear layer and ganglion cell layer. Doublelabeling showed that there was no costaining of pSTAT3 and glial fibrillary acidic protein (GFAP) in retina of control group, but there were many costained Muuml;ller cells in retinas treated with IL-1beta;.Conclusions Expression of pSTAT3 in Muuml;ller cells could be activated by IL-1beta; which may represent one pathway link to reactive gliosis.
Objective To observe the distribution and concentration of 125I-nerve growth factor (NGF) in rabbitsprime; eyes after intravitreal injection and posterior juxtascleral injection.Methods Intravitreal injection(group A) and posterior juxtascleral injection (group B) were performed with the dosage of 30mu;g/100mu;l 125I-NGF on left and right eyes in 45 white rabbits respectively. The gamma;-counts and the concentration of 125I-NGF (％ID/g) of each ocular tissue was determined 15 and 30 minutes, and 1,3,6,12,24,and 48 hours after injection. Results The 125I-NGF diffusion in group A was faster in ocular content and ocular inner wall. The vitreous content of 125I-NGF decreased gradually in group A, the curve changes in other eye tissues were normal. The concentration of 125I-NGF reached the peak 3 hours after injection in aqueous humor, iris and ciliary body, retina, and choroids, but 6 hours after injection in sclera and 8 hours in cornea. The changes of concentration of 125I-NGF in group B showed normal curve change. The peak time in group B were all 6 hours in all the tissues except aqueous humor (3 hours). Except the high concentration in vitreous body caused by intravitreal injection, the concentration of 125I-NGF in retina was the highest in group A. Conclusion Intravitreal injection of 125I-NGF can gain higher concentration in each ocular tissue than posterior juxtascleral injection, especially in retina. So intravitreal injection of NGF is a better ocular delivery method to treat the ocular fundus diseases.