Systemic application of sphingosine 1-phosphate receptor 1 immunomodulator inhibits corneal allograft rejection in mice.

PURPOSE: This study aims to investigate the effects of systemic application of sphingosine 1-phosphate receptor 1(S1P1) on allogeneic corneal transplantation in mice. METHODS: A total of 112 BALB/c mice received corneal grafts from C57BL/6 donors. Recipients were randomly divided into seven groups and treated with intraperitoneal injections of S1P1 (5 mg/kg/days), cyclosporine A (5 mg/kg/days), dexamethasone (1 mg/kg/days) and rapamycin (2 mg/kg/days). S1P1was combined with rapamycin or cyclosporine A, and saline served as negative control. Serum levels of IL-2, IL-10, TGF-ß1 and IFN-γ were measured by Elisa. The numbers of CD4+ T and regulatory (Treg) cell phenotype were measured by flow cytometry. Cytokine mRNA expression was analysed by real-time quantitative PCR. CD4+ T cells and cytokines were histologically identified by immunofluorescence staining. RESULTS: Corneal graft survival was prolonged by intraperitoneal injections in S1P1 alone (mean survival time MST, 35.3 ± 5.6 days), S1P1 combined with rapamycin (MST, 38.7 ± 6.5 days) or S1P1 and cyclosporine A (MST, 32.7 ± 4.8 days) compared with the controls (MST, 14.6 ± 0.2 days; n = 5, p < 0.01). S1P1 alone increased CD4+ T (p < 0.01) and Treg cells (p < 0.01; n = 5) in the cervical and mesenteric lymph nodes compared with the controls and S1P1 + rapamycin (p < 0.05; n = 5). TGF-ß1 and IL-10 mRNA transcriptions in corneal grafts following S1P1+ rapamycin increased (both p < 0.01; n = 3), and TGF-ß1 and IL-10 in the serum level following S1P1 alone increased (both p < 0.01; n = 3). These results paralleled the findings obtained from immunofluorescence. CONCLUSION: S1P1 has significant effect in corneal allograft rejection inhibition. The combined treatment of S1P1 and rapamycin results in synergistic effect.

Herniation of the retina in the central macula in an adult after iridocyclitis.

PURPOSE: To report an unusual case of retinal hernia in the central macula in an adult after iridocyclitis. CASE REPORT: We report a case of a 46-year-old male who presented with blurred vision 2 weeks after complete resolution of acute iridocyclitis. Anterior segment and vitreous body examinations were unremarkable. Yellowish spots in the macular area were observed. Spectral domain optical coherence tomography (SD-OCT) imaging of the macula showed loss of the inner segment/outer segment (IS/OS) photoreceptor junction, with irregularity of the retinal pigment epithelium (RPE), and a V-shaped hernia of the retina into the choroid. The macular lesions emerged as mild window defects on fluorescein angiography and were visualized as hypofluorescent patches on all-phase indocyanine green angiography. At a one month follow-up, the best-corrected visual acuity improved to 20/20, which was followed by partial restoration of the IS/OS line, but a V-shaped hernia of the retina remained unchanged on SD-OCT. CONCLUSION: Ophthalmologists should be alert to the changes in OCT of the macula in patients after iridocyclitis and further research on the cause and possible predisposing factors for retinal herniation is warranted.

Evaluation of tear malate dehydrogenase 2 in mild dry eye disease.

PURPOSE: To evaluate the effect of tear malate dehydrogenase 2 on monitoring ocular surface injury in mild dry eye (DE) disease. METHODS: A total of 15 DE patients (30 eyes) with mild subjective symptoms but no ocular surface fluorescein staining signs were enrolled in this study (DE group). The control group was 15 healthy age- and sex-matched volunteers (30 eyes). All subjects were asked to fill out a DE symptoms questionnaire and take different tests including tear MDH and MDH2 activities evaluation, tear breakup time (TBUT), Schirmer I, and slit-lamp examination of the ocular surface. We investigated different changes in tear MDH and MDH2 activities in the DE group and control group, discussed the association between tear MDH2 activity and DE symptoms, and the relationship between tear MDH2 activity and diagnostic tests (Schirmer I and TBUT). We also analyzed the changes in tear MDH2 activities after the treatment with artificial tears. RESULTS: Tear MDH activities in the DE group and control group were 288 ± 102 U/L and 259 ± 112 U/L, respectively, and this difference was not statistically significant (P > 0.05). The tear MDH2 activities in DE group were significantly increased compared with control group. Tear MDH2 was significantly and negatively correlated with the Schirmer's value (r = -0.733, P < 0.01) and the TBUT value (r = -0.841, P < 0.01). MDH2 also had a significant positive correlation with soreness symptoms (r = 0.687, P < 0.01). Treatment with artificial tears relieved or eliminated all discomfort symptoms, together with a considerable decrease in MDH2 activities (P < 0.01), but no significant changes in the Schirmer and the TBUT tests were observed. CONCLUSION: Tear MDH2 activity can indicate ocular surface injury in mild DE patients and may be used to monitor the response to therapy.

Valproic acid treatment inhibits hypoxia-inducible factor 1α accumulation and protects against burn-induced gut barrier dysfunction in a rodent model.

OBJECTIVE: Burn-induced gut dysfunction plays an important role in the development of sepsis and multiple organ dysfunction. Emerging evidence suggests that hypoxia-inducible factor-1α (HIF-1α) is critical in paracellular barrier functions via regulating vascular endothelial growth factor (VEGF) and myosin light chain kinase (MLCK) expression. Previous studies have also demonstrated that histone deacetylase inhibitors (HDACIs) can repress HIF-1α. This study aims to examine whether valproic acid (VPA), a HDACI, protects against burn-induced gut barrier dysfunction via repressing HIF-1α-dependent upregulation of VEGF and MLCK expression. METHODS: Rats were subjected to third degree 55% TBSA burns and treated with/ without VPA (300 mg/kg). Intestinal barrier dysfunction was evaluated by permeability of intestinal mucosa to fluorescein isothiocyanate (FITC)-dextran and histologic evaluation. Histone acetylation, tight junction protein zonula occludens 1 (ZO-1), VEGF, MLCK and HIF-1α were measured. In addition, CaCO2 cells were transfected with siRNA directed against HIF-1α and were stimulated with CoCl2 (1mM) for 24 hours with/without VPA (2mM) followed by analysis of HIF-1α, MLCK, VEGF and ZO-1. RESULTS: Burn insults resulted in a significant increase in intestinal permeability and mucosal damage, accompanied by a significant reduction in histone acetylation, ZO-1, upregulation of VEGF, MLCK expression, and an increase in HIF-1α accumulation. VPA significantly attenuated the increase in intestinal permeability, mucosa damage, histone deacetylation and changes in ZO-1 expression. VPA also attenuated the increased VEGF, MLCK and HIF-1α protein levels. VPA reduced HIF-1α, MLCK and VEGF production and prevented ZO-1 loss in CoCl2-stimulated Caco-2 cells. Moreover, transfection of siRNA directed against HIF-1α led to inhibition of MLCK and VEGF production, accompanied by upregulation of ZO-1. CONCLUSIONS: These results indicate that VPA can protect against burn-induced gut barrier dysfunction. These protective effects may be due to its inhibitory action on HIF-1α, leading to a reduction in intestinal VEGF and MLCK expression and minimizing ZO-1 degradation.

Ulinastatin suppresses burn-induced lipid peroxidation and reduces fluid requirements in a Swine model.

Objective. Lipid peroxidation plays a critical role in burn-induced plasma leakage, and ulinastatin has been reported to reduce lipid peroxidation in various models. This study aims to examine whether ulinastatin reduces fluid requirements through inhibition of lipid peroxidation in a swine burn model. Methods. Forty miniature swine were subjected to 40% TBSA burns and were randomly allocated to the following four groups: immediate lactated Ringer's resuscitation (ILR), immediate LR containing ulinastatin (ILR/ULI), delayed LR resuscitation (DLR), and delayed LR containing ulinastatin (DLR/ULI). Hemodynamic variables, net fluid accumulation, and plasma thiobarbituric acid reactive substances (TBARS) concentrations were measured. Heart, liver, lung, skeletal muscle, and ileum were harvested at 48 hours after burn for evaluation of TBARS concentrations, activities of antioxidant enzymes, and tissue water content. Results. Ulinastatin significantly reduced pulmonary vascular permeability index (PVPI) and extravascular lung water index (ELWI), net fluid accumulation, and water content of heart, lung, and ileum in both immediate or delayed resuscitation groups. Furthermore, ulinastatin infusion significantly reduced plasma and tissue concentrations of TBARS in both immediate or delayed resuscitation groups. Conclusions. These results indicate that ulinastatin can reduce fluid requirements through inhibition of lipid peroxidation.

Tissue-engineered epithelium transplantation for severe ocular surface burns.

PURPOSE: To evaluate the clinical outcomes of tissue-engineered epithelium transplantation for severe ocular surface burns. METHODS: This was a retrospective observational case series. From October 2005 to May 2011, 19 eyes of 19 patients with grade IV to VI ocular surface burns (Dua Classification) were treated by autologous transplantation of corneal stem cells cultivated on a fibrin gel membrane, with a mean follow-up of 16.2 months (range 12-36 months). Postoperative corneal surface stability, visual acuity (VA), corneal opacity, and neovascularization were evaluated. RESULTS: No corneal perforations occurred and the entire corneal surface was free from epithelial defects in all eyes. At the final follow-up visit, VA in 17 eyes was improved after surgery, with 6 eyes achieving a VA of 20/100 or better. Corneal vascularization was significantly reduced in 17 (89.5%) eyes. Corneal opacity was also improved in 12 (63.2%) eyes. All donor eyes remained healthy. CONCLUSION: Tissue-engineered epithelium transplantation can promote rapid reepithelialization of the ocular surface, inhibit corneal neovascularization, and improve vision for patients with severe ocular surface burns.

Clinical analysis of cataract surgery complicated by endophthalmitis.

PURPOSE: To assess the efficacy of vitrectomy combined with intravitreal injection in the treatment of endophthalmitis after phacoemulsification and IOL implantation. METHODS: Five patients (5 eyes), who had undergone conventional phacoemulsification combined with IOL implantation at another treatment facility, presented with endophthalmitis. The subjects ranged in age from 41 to 79 years (65.8 ± 0.5 years on average), and three were male. All five cases received bacterial culture susceptibility testing. On the basis of the treatment of primary disease, 3 cases had anterior chamber irrigation, and posterior vitrectomy followed by intravitreal injection of 1 mg vancomycin plus 2.25 mg ceftazidime. RESULTS: Four out of the five cases of endophthalmitis had a positive bacterial culture testing results (two cases of staphylococcus epidermidis, one case of enterococcus faecalis and one case of head-like staphylococcus), and the remaining case had no bacterial growth. Four cases showed restored visual acuity, clear vitreous cavity, and no retinal detachment or other complications. CONCLUSION: Management of patients presenting with endophthalmitis subsequent to cataract surgery should include: prompt bacterial culture and drug sensitivity tests, and where appropriate, vitrectomy combined with intravitreal injection of vancomycin.

The effect of Vaccinium uliginosum on rabbit retinal structure and light-induced function damage.

OBJECTIVE: To study the effect of Vaccinium uliginosum L., (VU) on the electroretinogram (ERG) and retinal pathological changes in rabbits after light-induced damage. METHODS: Twenty-eight Chinchilla rabbits were randomly divided into four groups: administration beforehand (A), administration after injury (B), light injury without administration (C), and blank (D) groups. After a 4-week administration of VU homogenate at 4.8 g/(kg·d) once a day in group A, ERG in groups A, B and C were recorded according to the standards set by the International Society for Clinical Electrophysiology of Vision (ISCEV). Except for group D, the groups were then exposed to strong light. Just after that, group A stopped receiving VU treatment and group B started to receive it. Then ERGs in all groups were recorded after 1 day, 1 week, and 2 weeks. Throughout the whole process groups which were not fed with VU were fed with normal saline. Finally, the tissues and structures of all the groups were observed and the thickness of the outer nuclear layers (ONL) was measured. RESULTS: (1) After 4-week feeding with VU, the latency time of ERG in group A became shorter than those in the other groups and the amplitude increased. After being exposed to strong light, the latency time lengthened and amplitude decreased in all the injury groups, but comparing at each time point, the measured values in group A were better than those in group C. With the accumulation of VU, the ERG in group B improved, and finally, all of the detected values became better than those in group C. (2) Retinae in group D were normal in histology and the layers were in order but those in group C became disarranged. The injuries in groups A and B were minor compared with those in group C. The thickness of the ONL in group C was significantly thinner than in the other groups (P=0.000), and that in groups A and B was thicker than that in group C, although thinner than in group D. That in group A was thicker than in group B. CONCLUSIONS: VU can relieve the injury to rabbit retinae exposed to normal day and night rhythm, alleviate the harm caused by light when used beforehand, and repair the light damage to the retina.

Effect of amnion membrane transplantation on corneal neovascularization in 10 patients with alkali burn.

By observing clinical cases, we studied the curative effect of amnion membrane transplantation on decreasing corneal neovascularization (CNV). It was a non-randomized retrospective case-control study. Among 17 cases (21 eyes) of third-degree alkali burns from 2007 to 2010, 10 cases (12 eyes) were performed with amnion membrane transplantation operation, and others were not. Amnion membrane transplantation was performed at the 3(rd) day after burn in the treatment group. Areas of CNV in double groups were measured at the 14(th) day and 60(th) day after burn. Area of CNV in the treatment group was (66.207±7.251)mm(2) at the 14(th) day after burn, and was 18.27% lower than that in the control group. Area of CNV in the treatment group was (120.046±13.812)mm(2) at the 60(th) day after burn, and was 11.35% lower than that in the control group. There was both statistical significance (P<0.05). Amnion membrane transplantation operation can inhibit the growth of corneal neovascularization induced by alkali burn.

[Clinical study of the effect of amnion membrane transplantation on diminishing corneal neovascularization induced by alkali burn].

PURPOSE: To study the curative effect of amnion membrane transplantation on decreasing corneal neovascularization(CNV) induced by alkali burn. METHODS: It was a non-randomized retrospective case-control study. Among 19 cases (23 eyes) of third-degree alkali burns from 2006 to 2010, 11 cases (13 eyes) were performed with amnion membrane transplantation operation, and others were not. Amnion membrane transplantation was performed at 3rd day after burns in the treatment group. Ages and treatments beyond surgery of double groups were matched. Areas of CNV in double groups were measured at the 14th and 60th days after burn. RESULTS：Area of CNV in the treatment group was (62.133±8.571) mm² at the 14th day after burn, and was 30.6% lower than that in the control group. Area of CNV in the treatment group was (112.019±17.362)mm² at the 14th day after burn, and was 13.5% lower than that in the control group. There was statistical significance between the two groups (P<0.05). CONCLUSION: Amnion membrane transplantation operation can inhibit the growth of corneal neovascularization induced by alkali burn.

[Relationship between retinal neurons apoptosis and changes of manganese superoxide dismutase activity and mRNA expression in early diabetic rats].

OBJECTIVE: To study the relationship between the apoptosis of retinal neurons and changes of manganese superoxide dismutase (MnSOD) activity and mRNA expression in early diabetic rats. METHODS: Controlled experimental study. Seventy two male 8-week-aged SD rats were divided into control group and diabetic mellitus group. Each group were subdivided into 4, 8 and 12 weeks groups (each group, n = 12). The diabetic group rats were injected with a single dose of streptozotocin (60 mg/kg) to induce the diabetic model, the control group rats were raised without any intervention. Apoptosis of retinal neurons was detected by TdT-mediated dUTP nick end label (TUNEL) assay. The protein expression of caspase-3 was detected by immunohistochemistry. Xanthine oxidase method was used to measure the activity of MnSOD and copper-znic superoxide dismutase (Cu-ZnSOD). MnSOD mRNA, Cu-ZnSODmRNA and caspase-3 mRNA levels were determined by SYBR Green Realtime PCR Master Mix. ANOVA was used to test the comparisons of the apoptosis ratio of retinal ganglion cells, the levels of caspase-3 mRNA, and the activity and mRNA levels of Cu-ZnSOD and MnSOD in the control groups and the diabetic groups, and LSD was used to test multiple comparisons. RESULTS: (1) The difference of the retinal ganglion cells apoptosis ratio in the control groups and the diabetic groups had statistical significance at 4, 8, 12 weeks (F = 19.5412, P < 0.05). There were no apoptosis neurons in control groups' retina at 4, 8, 12 weeks. Apoptosis of the retinal neurons occurred 4 weeks after the onset of diabetes. The apoptosis ratio of retinal ganglion cells in rats that had diabetes for 8 and 12 weeks was (5.7 +/- 3.9)% and (11.8 +/- 5.1)%, respectively, and was significantly higher than that of age-matched control groups (8 and 12 weeks: P = 0.000). (2) Caspase-3 protein expression was not observed in the control rats' retina at 4, 8, 12 weeks. Positive staining of caspase-3 occurred 4 weeks after the onset of diabetes, and enhanced at 8 and 12 weeks. The difference of caspase-3 mRNA levels in the control groups and the diabetic groups had statistical significance at 4, 8, 12 weeks (F = 105.175, P < 0.05). In control rats at 4, 8 and 12 weeks, caspase-3 mRNA levels were 1.649 +/- 0.586, 1.526 +/- 0.486, 1.614 +/- 0.296, respectively. Caspase-3 mRNA levels in diabetic rats that had diabetes for 4, 8 and 12 weeks were 5.672 +/- 1.193, 12.566 +/- 2.272, 14.297 +/- 2.11, respectively, which were greater than that in the control groups (4, 8 and 12 weeks: P = 0.000). (3) The difference of the activity and mRNA levels of MnSOD and Cu-ZnSOD in the control groups and the diabetic groups had statistical significance at 4, 8, 12 weeks (MnSOD: activity: F = 19.709, P < 0.05, mRNA: F = 93.352, P < 0.05; Cu-ZnSOD: activity: F = 16.708, P < 0.05, mRNA: F = 16.332, P < 0.05). In the control groups at 4, 8 and 12 weeks, the activity of MnSOD was (47.118 +/- 5.018), (46.033 +/- 6.835) and (45.813 +/- 6.859) U/mg, respectively; and MnSOD mRNA levels were 0.973 +/- 0.123, 0.974 +/- 0.085 and 0.994 +/- 0.074, respectively. The activity of Cu-ZnSOD was (113.884 +/- 9.07), (112.301 +/- 5.24) and (117.52 +/- 7.982) U/mg, respectively; and Cu-ZnSOD mRNA levels of were 1.067 +/- 0.109, 1.055 +/- 0.119, 1.092 +/- 0.180, respectively. In the rats that had diabetes for 4, 8 and 12 weeks, the activity of MnSOD was (33.863 +/- 6.909), (22.877 +/- 7.875) and (20.034 +/- 6.796) U/mg, respectively; and MnSOD mRNA levels were 0.627 +/- 0.083, 0.333 +/- 0.080, 0.256 +/- 0.057, respectively; these data were less than those in the age-matched control groups (activity: 4 weeks: P = 0.002, 8 and 12 weeks: P = 0.000; mRNA: 4, 8 and 12 weeks: P = 0.000). The activity (109.793 +/- 7.468) U/mg and mRNA level (0.976 +/- 0.108) of Cu-ZnSOD in rats had diabetes for 4 weeks showed no significant difference as compared to age-matched control group (activity: P = 0.426; mRNA: P = 0.172). In diabetic rats at 8 and 12 weeks, the activity of Cu-ZnSOD was (98.588 +/- 9.212) and (78.168 +/- 12.180) U/mg, respectively; Cu-ZnSOD mRNA levels were 0.829 +/- 0.048 and 0.621 +/- 0.033, respectively; these data were less than those in the age-matched control group (activity: 8 weeks: P = 0.011, 12 weeks: P = 0.000; mRNA: 8 weeks: P = 0.001, 12 weeks: P = 0.000). The changes of MnSOD occurred as early as 4 weeks after the onset of diabetes, while the changes of the Cu-ZnSOD occurred later, mainly at 8 and 12 weeks after the onset of diabetes. CONCLUSIONS: Apoptosis of the retinal neurons in early diabetic rats may correlate with the decline of the activity and mRNA expression of MnSOD.

[The effect of Vaccinium uliginosum to the electroretinogram and retina of rabbits before and after light-induced damage].

OBJECTIVE: Study the effect of Vaccinium uliginosum (VU) on the electroretinogram (ERG) and histology of rabbits' retina before and after light-induced damage. METHODS: It was an experimental study in contrast. Thirty-five Chinchilla Rabbits were divided into five groups according to the randomization tables. All rabbits ate and drank freely except those in group A and D who were fed with VU homogenate. Four weeks later we observed the tissue & structure of the rabbits in group D and E under the light microscope and measured the thickness of their out nuclear layers (ONL) and apoptosis index (AI). At the same time, we recorded maximal combined reaction ERG and oscillatory potentials (oscillatory potentials, OPs) of the left rabbits according to the standards set by the International Society for Clinical Electrophysiology of Vision (ISCEV). Then group A, B and C were exposed to strong light. Also we stopped feeding group A with VU and start to feed group C with it. We recorded ERG of them all after 1 day, 1 week and 2 weeks respectively. Then we observed the tissues & structures of them. SPSS 12.0 software package was used for one-way or double ways ANOVA and LSD test. RESULTS: (1) Maximal combined reaction ERG: after four weeks feeding implicit time of group A: a wave (14.079+/-0.841) ms, b wave (35.629+/-6.865) ms; amplitude: a wave (83.936+/-10.807) microV, b wave (280.931+/-27.807) microV. Two weeks after injury implicit time of group A: a wave (15.571+/-1.087) ms, b wave (38.915+/-7.683) ms, amplitude:a wave (66.478+/-9.709) microV, b wave (245.887+/-11.797) microV. After four weeks feeding implicit time of group B: a wave (15.635+/-1.661) ms, b wave (42.985+/-3.164) ms; amplitude: a wave (69.331+/-12.355) microV, b wave (197.331+/-16.157) microV. Two weeks after injury implicit time of group B: a wave (18.783+/-1.966) ms, b wave (52.322+/-4.784) ms, amplitude:a wave (57.562+/-8.217) microV, b wave (159.569+/-17.859) microV. After four weeks feeding implicit time of group C: a wave (15.115+/-0.940) ms, b wave (43.242+/-4.662) ms, amplitude: a wave (72.812+/-4.403) microV, b wave (207.815+/-14.373) microV. Two weeks after injury implicit time of group C: a wave (15.957+/-2.154) ms, b wave (44.081+/-9.506) ms, amplitude: a wave (66.804+/-8.755) microV, b wave (186.271+/-29.349) microV. These three groups had statistical significance in maximal combined reaction ERG (implicit time of a wave: fed 4 weeks F=6.057, P<0.05; two weeks after injury F=13.296, P<0.05. Implicit time of b wave: fed 4 weeks F=9.949, P<0.05; two weeks after injury F=11.145, P<0.05. Amplitude of a wave: fed 4 weeks F=8.468, P<0.05; two weeks after injury F=4.844, P<0.05. Amplitude of b wave: fed 4 weeks F=70.194, P<0.05; two weeks after injury F=62.161, P<0.05). The total amplitudes of OPs (OPs=OPs1+OPs2+OPs3) of them had statistical significance (fed 4 weeks F=17.482, P<0.05; two weeks after injury F=11.748, P<0.05). By LSD test we found that before injury the amplitude of a wave and b wave in group B and C in maximal combined reaction ERG were significantly lower than those of group A which was fed by VU for 4 weeks (the a wave and b wave of group B compared to A: P=0.003, 0.000; the a wave and b wave of group C compared to A: P=0.001, 0.000). After light-induced injury, the implicit time of all the groups was increased and amplitude was decreased. But after the injury time of 1 day, 1 week and 2 weeks, the amplitude of b wave of group A was respectively (229.743+/-11.978) microV, (212.785+/-21.021) microV, (245.887+/-11.797) microV, which was significantly higher than group B in the same period (P=0.000). With the accumulation of VU the ERG of group C was improving. Two weeks after injury the implicit time of b wave in group C was (44.081+/-9.506) ms and the amplitude was (186.271+/-29.349) microV. Compared with group B the former was decreased and the latter was increased significantly (implicit time: P=0.008; amplitude: P=0.007). (2) Group D and E were normal in histology and layers were in order. While group B got disordered. Group A and C were injured slightly. The thickness of ONL among all groups had statistical significance (F=330.506, P<0.05). (3) There was statistical significance among all groups in AI (F=230.126, P<0.05). AI of group B was (10.960+/-1.534)% and was higher than others' (P=0.000). AI of group D was (1.817+/-0.203)% and lower than group E (P=0.000). CONCLUSIONS: Vaccinium uliginosum can decrease retinal cell apoptosis and reduce photochemical damage to retinal tissue. In addition VU is able to promote retinal repairing after light damage.

[Ocular manifestations of brainstem tumor].

OBJECTIVE: To investigate the ocular manifestations of brainstem tumors and to avoid misdiagnosis and missed diagnosis. METHODS: This is a retrospective case series study. The clinical data of 57 brainstem tumor in-patients were collected from 1993 to 2007. The clinical manifestations and the results of related examinations were analyzed. RESULTS: The present series included 51 cases of brainstem germinoma, 4 cases of cavernous hemangioma, 1 case of hemangioblastoma and 1 case of metastatic tumor. In 51 cases of brainstem germinoma, there were 37 males and 14 females. The first attack age varied from 5 to 55 years old and the median age was 23 years old. The high incident ages of brainstem germinoma were 10 - 35 years. Patients were presented with diplopia, ocular motility disturbance, nystagmus, anisocoria, and facial palsy. In 57 patients, diplopia was the initial symptom in 12.3% (7/57) cases. The incidence of oculomotor nerve paralysis was 17.5% (10/57); trochlear paralysis, 1.8% (1/57); trigeminal nerve paralysis, 5.3% (3/57); abducens nerve paralysis, 35.1% (20/57); facial palsy, 14.0% (8/57); optic disc edema, 19.3% (11/57); nystagmus, 21.1% (12/57) and anisocoria, 10.5% (6/57). CONCLUSIONS: Ocular manifestations occur frequently in brainstem tumor. Nuclear ophthalmoplegia, nystagmus and other neuro-ophthalmic signs provide helpful clues for the diagnosis of brainstem tumor.

Differential regulation of dentin matrix protein 1 expression during odontogenesis.

Dentin matrix protein 1 (DMP1) is highly expressed in mineralized tooth and bone. Both in vitro and in vivo data show that DMP1 is critical for mineralization and tooth morphogenesis (growth and development). In this study, we studied Dmp1 gene regulation. The in vitro transient transfection assay identified two important DNA fragments, the 2.4- and 9.6-kb promoter regions. We next generated and analyzed transgenic mice bearing the beta-galactosidase (lacZ) reporter gene driven by the 2.4- or 9.6-kb promoter with the complete 4-kb intron 1. The 9.6-kb Dmp1-lacZ mice conferred a DMP1 expression pattern in odontoblasts identical to that in the endogenous Dmp1 gene. This is reflected by lacZ expression in Dmp1-lacZ knock-in mice during all stages of odontogenesis. In contrast, the 2.4-kb Dmp1-lacZ mice display activity in odontoblast cells only at the early stage of odontogenesis. Thus, we propose that different transcription factors regulate early or later cis-regulatory domains of the Dmp1 promoter, which gives rise to the unique spatial and temporal expression pattern of Dmp1 gene at different stages of tooth development.