Objective To explore the effect of oxygen inhalation on the retinae of newborn rats and its mechanism.Methods We mimicked the retinopathy of prematurity(ROP) by putting the newborn rats in high concentrated oxygen. One-day old rats were put into the oxygen box with the oxygen concentration of 80% for continuous 7 days; then in air condition for 7 days. The arterial blood oxygen pressure, retinal superoxide dismutase (SOD), and malondialdehyde (MDA) of the rats (1,2,4,7,8,9,11,14 days old) were examined. The diameter of retinal vessels′main branch and the coverage rate of peripheral vessels were measured in 7- and 14-day-old rats by ink perfusion. The retinal neovascularization of rats (8,9,11, 14 days old) were observed by HE staining. The rats of the same age fed in air condition were in the control group.Results The differential pressures of blood oxygen of rats (1,2,4,7 days old) in study group were significantly higher than those in the control group (P＜0.01), while the differential pressures of blood oxygen of rats (8,9,11,14 days old) in study group were lower than those in the control group (P＞0.05). The contents of SOD of the retinae in the rats ( 1,2,4,7,8 days old) were significantly lower than those in the control group(P＜0.01, P＜0.05 ), while the contents of MDA were significantly higher than those in the control group (P＜0.01,P＜0.05). The diameter of retinal vessels′main branch in 7-day rats was 75% of the control group, and the coverage rate of peripheral vessels was 22% of the control group; and was 61% and 73% respectively in 14-day-old rats. The neovascularization could be seen in 16.7% of the rats in the study group and nought in the control group.Conclusion The damage of free radical of the retina in high concentrated oxygen and hypoxia situation after oxygen supply may be one of the most important mechanism of ROP. (Chin J Ocul Fundus Dis，2003，19：269-332)
Objective To investigate the interference effect of nerve growth factor (NGF) on apoptosis of retinal cells in experimental retinal detac hment (RD). Methods Twenty seven Sprague-Dawely rats were selected, and the left and right eyes were in the experimental control group and NGF group, respectively. After the RD model was set up by subretinal injection with sodium hyaluronate, 5mu;l NGF（1mu;g/mu;l）was injected into the vitreous body of the right eyes which were in the NGF group; 5mu;l PBS was injected into vitreous body of left eyes which were in the experimental control group. The injection was performed once every 4 days till the end of the observation period. The eye balls of the 27 rats were extrafted 1.5, 3, 6, 12 hours, 1 day, 2, 4, 8 , 16, and 32 days after the RD model was established. Another 2 rats were selected as the normal control, which underwent none of the injections but eyeball extraction at the end of the observation period. TUNEL and transmission electron microscopy were used to detect the apoptosis of the retinal cells. Cell counts and statis tical analysis were used to assess results. Results Typical apoptosis cells were observed in the early time of RD. Apoptosis was found in each retinal layers, especially in inner and outer nuclear layers. The number of apoptosis cells increased as the time of RD was prolonged（Plt;0.01）. It was also found that apoptosis cells in NGF group were less than that in the experimenta l control group（Plt;0.01）. Conclusion Intravitreous injection exogenous NGF may inhibit the apoptosis of retinal cells in experimental RD. (Chin J Ocul Fundus Dis, 2006, 22: 333-335)
Objective To observe the change of diffusion upper limit of macromol ecules through pathological retina and the difference between the layers of retina. Methods Retinal edema was emulated by establishing branch retinal vein occlusion (RVO) model in miniature pig eyes under photodynamic method. Two days later, the retinas of both eyeballs were peeled off. The diffusion test apparatus was designed by ourselves. FITC-dextrans of various molecular weights (4.4, 9.3, 19.6, 38.9, 71.2 and 150 kDa) and Carboxyfluorescein (376 Da) were dissolved in RPMI1640 solutions and diffused through inner or outer surface of retina. The rate of transretinal diffusion was determined with a spectrophotometer. Theoretical maximum size of molecule (MSM) was calculated by extrapolating the trend-linear relationship with the diffusion rate. In separate experiments to determine the sites of barrier to diffusion, FITC-dextrans were applied to either the inner or outer retinal surface, processed as frozen sections, and viewed with a fluores cence microscope. Results FITC-dextrans applying to inner retinal surface, 4.4 kDa dextrans were largely blocked by inner nuclear layer (INL); 19.6,71.2 kDa dextrans were blocked by the nerve fiber layer (NFL) and inner plexiform layer; 15.0 kDa dextrans were blocked by NFL. FITC-dextrans applying to outer retinal surface, most dextrans with various molecular weights were blocked before outer nuclear layer (ONL). No matter applying to the inner or outer surface, Carboxyfluore scein can diffuse through the whole retina and aggregate at INL and ONL. After RVO, the inner part of retina became edema and cystoid, loosing the barrier function. Compared with the normal retina, the MSM in RVO tissues increased (6.5plusmn;0 39nm Vs 6.18plusmn;0.54nm, t=4.143, P=0.0001). Conclusions A fter RVO, the barrier function of inner part of retinal is destroyed and the upper limit of diffusion macromolecule size increased, which is nevertheless limited. ONL acts as bottle-neck barriers to diffusion, if the outer part of retina is damaged, the change of the diffusion upper limit will be prominent. （Chin J Ocul Fundus Dis，2008，24：197-201）
Objective To investigate the effects of intravitreal injection of matrix metalloproteinase-3 (MMP-3) on the vitreoretinal adhesion and the vitreous gelatin. Methods Twenty-four pigmented rabbits were randomly divided into 3 experimental groups（group A, B, and C）and one control group with 6 rabbits (12 eyes) in each. Different concentrations of 0.1 ml MMP-3 (5,10, 20 ng in group A, B, and C, respectively) and equivalent dose of balanced salt solution were intravitreally injected to the rabbits, respectively. Clinical examinations (such as gross observation, slit-lamp biomicroscopy, indirect fundus ophthalmoscopy ), electroretinography (ERG) and fundus fluorecein angiography (FFA) were taken before and after injection. Results One week after injection, posterior vitreous detachment (PVD) and focal vitreous liquefaction were recognized clinically for the first time in 1 eye in group B. By the end of this study, clinically detected PVD developed in 1 eye in group A, 3 eyes in group B, but the synchisis developed slowly, and no liquefaction or PVD occurred in control group. As for the histological examination, partial PVD was observed in 1 eye in group A and 3 eyes in group B 60 minutes after injection. All of the eyes in group A and B showed partial PVD 1 week after injection, and the area of PVD enlarged in contrast with before. Complete PVD were recognized in 1 eye in group A and 3 eyes in group B 15 weeks after injection, and the cleavage was narrow and limited. In group C, inflammatory cell infiltration in the inner layer of retina, destruction of retinal structure, and fluorescein leakage at late phase was found in the early period after injection. Conclusions MMP-3 is effective in disrupting the adhesion of the posterior hyaloid to the inner limiting membrane leading to PVD, and helpful to some extent in producing vitreous liquefaction. The dose of 10 ng MMP-3 is safe and effective for the rabbits eyes, which may be used as an promising assistant of vitreous surgery. (Chin J Ocul Fundus Dis，2004，20：67-132)
Objective To evaluate the expressive varieties of Nogo-A mRNA in injured optic nerves of rats. Methods Reverse transcription polymerase chain reaction (RT-PCR) method was used to hemi-quantitatively analyze the levels of Nogo-A mRNA in the optic nerves 3, 7, 9, 15, 21, and 25 days respectively after injury.Results The level of the expression of Nogo-A mRNA was low in the normal optic nerves, while it was significantly high in the optic nerves 3 days after in jury, and kept the high level still after 25 days.Conclusion The expression of Nogo-A mRNA in injured optic nerves is increased. (Chin J Ocul Fundus Dis，2003，19：201-268)
Objective It has been shown that pigment epitheliumderived factor (PEDF) is an effective anti-apoptosis agent on several kinds of cells of the central nervous system.This study aimed to evaluate the effect of PEDF on pressure induced retinal ischemia in a rat model. Methods Retinal ischemia was induced by increasing the intraocular pressure to 110 mm Hg for 45 minutes via an intracameral catheter.Ten microlit ers (0.1 mu;g/mu;l) PEDF was injected into the vitreous of 4 eyes of each group im mediately after reperfusion and 4 additional eyes received only normal saline as vehicle controls.The animals were euthanized at 2 or 7 days after reperfusion.T he effect of PEDF on retinal degeneration was assessed by measuring the thicknes s of the inner retinal layers (MTIRL) and counting the retinal ganglion cells (R GC) on plastic embedded retinal sections. Results The MTIRL and the RGC counting in eyes treated with intravitreal PEDF were significantly higher than those in vehicle controls (118.1plusmn;5.0) mu;m vs(94.9plusmn;3.0) mu;m (Plt;0.05);(6.0plusmn;1.0) cells/100 mu;m vs (4.5 plusmn;0.5) cells/100 mu;m (Plt;0.05) 7 days after reperfusion,respectively． Conclusion Intravitreal administration of PEDF can ameliorate an ischemiareperfusion retinal injury and may be useful to prevent neuronal degeneration in the inner retina. (Chin J Ocul Fundus Dis, 2001,17:138-140)
ObjectiveTo observe the inhibitory effect of endostatin (ES) on oxygen-induced retinal neovascularization.MethodsThirtyfour 7-day-old C57BL/6J mice were randomly divided into 3 groups: oxygen-exposed group (12 mice), ES group (12 mice) and the control group (8 mice). The mice in oxygen-exposed and ES group were exposed to (75±5)％ oxygen for 5 days and then back to the normal air. In ES group, 1 μg ES endostatin were injected into vitreous in one eye, while PBS was injected into the other eye as the control 12 and 36 hours after being exposed to oxygen. The mice in the control group were fed in normal circumstance. The changes of retinal neovascularization was examined by fluorescence angiography with fluorescein isothiocyanatedextran. The number of endothelial cells breaking through the internal limiting membrane (ILM) was counted and the inhibitory effects of ES on retinal neovascularization was observed.ResultsCompared with the oxygen-exposed group, the branches of retinal vessels went normal without any un-perfused area in ES group. The number of nuclei of endothelial cells breaking through ILM on each retinal crosssection decreased to (5.39±1.52), which differed much from that in the oxygen-exposed group (22.56±2.13) (plt;0.001).ConclusionES can effectively inhibit the formation of retinal neovascularization in rats and might be a new path of the treatment for proliferative retinopathy.(Chin J Ocul Fundus Dis, 2005,21:314-317)