Bright light therapy (BLT) has been proved to have beneficial effects on Parkinson’s disease (PD), the mechanisms remained unclear. Improvements of visual pathways might be key to BLT. The aim of this study is to validate whether BLT improves clinical symptoms in PD and explore the possible mechanisms of visual pathways evaluated by optical coherence tomography (OCT), pattern electroretinogram (PERG) and visual evoked potentials (VEP). Twenty-three PD patients were enrolled in this crossover randomized placebo-controlled study. Participants received either one month of BLT or dim light therapy (DLT), separated by one-month wash-out period, followed by another intervention. Participants underwent clinical scales, and visual-related evaluations including OCT, PERG and VEP before and after each intervention. Mixed-effects regression models were used to determine the effect between BLT and DLT on improving the differentials of clinical scales (Δscales), OCT (Δretinal thickness), PERG (ΔPERG values) and VEP (ΔP100 latencies). Correlations between clinical symptoms and visual evaluations improvements were analyzed in PD patients receiving BLT. Excessive daytime sleepiness, anxiety, life quality and autonomic function were improved after BLT. Compared with DLT, bilateral ΔN95 latencies for PERG and ΔP100 latencies for VEP were improved after BLT. We did not observe the changes of four quadrants retinal nerve fiber layer (RNFL) thickness after BLT or DLT. BLT is a valuable and safe non-pharmacological intervention for improving visual function in PD patients. These findings extend neural mechanisms of BLT to visual pathways improvements.
Vascular endothelial growth factor (VEGF) signaling is crucial for choroidal neovascularization (CNV), a major pathological feature of neovascular age-related macular degeneration (nAMD). Gene transcription of VEGF is mainly regulated by hypoxia-inducible factor 1-alpha (HIF-1α). The chromobox (CBX) family polycomb protein (Pc) subgroup includes CBX2, CBX4, CBX6, CBX7, and CBX8. CBX4 enhances hypoxia-induced VEGF expression and angiogenesis in hepatocellular carcinoma (HCC) cells by increasing HIF-1α’s transcriptional activity. The objective of the study was to examine the functions of members of the CBX family Pc subgroup in choroidal vascular endothelial cells (CVECs) during CNV. CBX4 and CBX7 expression was up-regulated in hypoxic human choroidal vascular endothelial cells (HCVECs). In HCVECs, CBX7 facilitated HIF-1α transcription and expression, while CBX4 did not. In HCVECs, CBX7 stimulated HIF-1α's nuclear translocation and transcriptional activity, which in turn stimulated VEGF transcription and expression. The CBX7/HIF-1α/VEGF pathway promoted the migration, proliferation, and tube formation of HCVECs. The CBX7/HIF-1α/VEGF pathway was up-regulated in CVECs and in the mouse model with laser-induced CNV. Mouse CNV was lessened by the blockade of CBX7 through the down-regulation of HIF-1α/VEGF. In conclusion, CBX7 enhanced pro-angiogenic behaviors of hypoxic CVECs by up-regulating the HIF-1α/VEGF pathway, which contributing to the formation of mouse laser-induced CNV.
Objective:To investigate the mechanism of curcumin in the treatment of diabetic retinopathy (DR) by network pharmacology and molecular docking.Methods:The compounds targets of curcumin were predicted by SEA and SwissTargetPrediction databases, and the DR target genes were obtained by CTD database.The different genes were mapped and matched by Venny database to screen their intersections.The intersecting genes were submitted to GeneMANIA database to construct a protein-protein interaction network.WebGestalt database was used to conduct enrichment analysis and AutoDock Vina was used to perform molecular docking of the core targets.Results:A total of 52 targets of curcumin, 1 599 targets of DR and 48 intersecting targets were detected.The core targets were serine/threonine-protein kinase 1 (AKT1), tumor necrosis factor-α (TNF-α), epidermal growth factor receptor (EGFR), signal transduction and activator of transcription 3 (STAT3) and heat shock protein 90 alpha family class A member 1 (HSP90AA1). Enrichment analysis suggested that these targets were mainly associated with signaling pathways, including the EGFR tyrosine kinase inhibitor resistance signaling pathway, hypoxia-inducible factor-1 (HIF-1) signaling pathway, interleukin (IL)-17 signaling pathway and advanced glycosylation end product-the receptor of advanced glycosylation end product (AGE-RAGE) signaling pathway.Conclusions:Curcumin may play an important role in the treatment of DR by regulating multiple signaling pathways to inhibit the inflammatory response and combat oxidative stress.
Wet age‐related macular degeneration (wAMD), characterized by choroidal neovascularization (CNV), is a leading cause of irreversible vision loss among elderly people in developed nations. Subretinal fibrosis, mediated by epithelial‐mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells, leads to unsuccessful anti‐vascular endothelial growth factor (VEGF) agent treatments in CNV patients. Under hypoxic conditions, hypoxia‐inducible factor‐1α (HIF‐1α) increases the stability and activation of p53, which activates microRNA‐34a (miRNA‐34a) transcription to promote fibrosis. Additionally, Klotho is a target gene of miRNA‐34a that inhibits fibrosis. This study aimed to explore the role of the HIF‐1α/p53/miRNA‐34a/Klotho axis in subretinal fibrosis and CNV. Hypoxia‐induced HIF‐1α promoted p53 stability, phosphorylation and nuclear translocation in ARPE‐19 cells (a human RPE cell line). HIF‐1α‐dependent p53 activation up‐regulated miRNA‐34a expression in ARPE‐19 cells following hypoxia. Moreover, hypoxia‐induced p53‐dependent miRNA‐34a inhibited the expression of Klotho in ARPE‐19 cells. Additionally, the HIF‐1α/p53/miRNA‐34a/Klotho axis facilitated hypoxia‐induced EMT in ARPE‐19 cells. In vivo, blockade of the HIF‐1α/p53/miRNA‐34a/Klotho axis alleviated the formation of mouse laser‐induced CNV and subretinal fibrosis. In short, the HIF‐1α/p53/miRNA‐34a/Klotho axis in RPE cells promoted subretinal fibrosis, thus aggravating the formation of CNV.
AIM: To investigate the changes of Iba-1 and other potential markers for microglia activation in experimental diabetic retinopathy (DR). METHODS: Male Sprague-Dawley rats were rendered diabetes via intraperitoneal injection of streptozotocin. The retinas were harvested at 1 to 24wk after diabetes onset. Hypoxia-treated mouse microglial cell line (BV2 cells) was employed as the in vitro model to mimic diabetic condition. The expressions of Iba-1, CD11b, ICAM-1 as well as the inflammatory factors were examined with real-time polymerase chain reaction, Western blot and immunofluorescence both in vivo and in vitro. RESULTS: Compared with age-matched normal control, the number of microglia (Iba-1 positive immunostaining) in diabetic rat retinas was increased from 1 to 24wk of diabetes, which was most obvious at 12wk of diabetes. Iba-1 protein expression detected by Western blot was increased slightly in diabetic rat retinas compared with that in age-matched normal control; however, there was statistically significant between two groups only at 2wk after diabetes onset. The mRNA expression of Iba-1 was decreased significantly at 2 and 4wk of diabetic rat retinas, and remained unchanged at 8 and 12wk of diabetes. In BV2 cells, there was no significant change for the Iba-1 protein expression between normoxia and hypoxia groups; however, its mRNA level was decreased significantly under hypoxia. To further characterize microglial activation, F4/80, CD11b and inflammatory factors were detected both in vivo and in vitro. Compared with normal control, the expressions of F4/80 and CD11b as well as the inflammatory factors, such as ICAM-1, iNOS, COX2, IL-1β and IL-6, were increased significantly both in vivo and in vitro. CONCLUSION: Iba-1 protein expression might not be a sensitive marker to evaluate the activation of microglia in experimental DR. However, Iba-1 immunostaining, in combination with other markers like CD11b and ICAM-1, could be well reflect the activation of microglia. Thus, it is of great importance to explore other potential marker to evaluate the activation of microglia.
Objective:To investigate the effects of leukocyte common antigen-related phosphatase receptor (LAR) on the regulation of visual plasticity in rats.Methods:Fourty newborn Wistar rats were randomly divided into 5 groups, with 8 rats in each group, and were executed at 1 week, 3, 5, 7 and 9 weeks postnatal, respectively.Thirty-two healthy and 10-week-old Wistar rats were randomly divided into a normal control group, a fluoxetine group, a binocular form deprivation (BFD) group and a BFD+ fluoxetine group, with 8 rats in each group.Rats in the fluoxetine group drinked water with the dosage of 0.2 mg/ml fluoxetine for 4 weeks.The rats in the BFD group received eyelids suture for 2 weeks to form BFD model.And the combination of fluoxetine administration and BFD was performed in the BFD+ Fluoxetine group.No intervention was conducted in the normal control group.The expressions of LAR and chondroitin sulfate proteoglycans (CSPGs) were detected by immunofluorescence.The expression of LAR in the visual cortex of rats was detected by Western blot.Results:LAR was distributed in the cell membrane, plasma and axon.CSPGs were distributed in the intercellular substance in visual cortex of rats.The fluorescence intensities of LAR and CSPGs increased with the postnatal development.The relative expression of LAR was (100.00±3.20)%, (108.37±2.26)%, (113.69±2.33)%, (131.83±3.78)% and (140.11 ±4.02)% at 1 week, 3, 5, 7 and 9 weeks postnatal, respectively, the difference was statistically significant ( F=31.70, P=0.001). The relative expression of LAR was increased according to the growth of age ( β=0.961, P=0.007). The relative expression of LAR was(100.00±2.96)%, (81.02±2.77)%, (71.99±3.09)% and (52.90±2.01)% in the normal control group, fluoxetine group, BFD group and fluoxetine+ BFD group, respectively, with a significantly difference among the groups ( F=18.16, P=0.015), the relative expressions of LAR protein in the fluoxetine group, BFD group and BFD+ fluoxetine group were significantly lower than that in the normal control group ( t=31.30, 36.10, 41.72; all at P<0.01). Conclusions:LAR may be involved in the regulation of visual plasticity as a specific receptor of CSPGs.
Objective:To investigate the effects of anemoside B4 on apoptosis of retinal cells in diabetic rats.Methods:Sixty Sprague-Dawley rats were randomized into three groups: the normal control(control), diabetic rats(DM)and diabetic rats treated with Anemoside B4(B4)groups(n=20, each group). Rats in the DM and B4 groups were rendered diabetic with an intraperitoneal injection of streptozotocin(STZ, 60 mg/kg). After 3 days of successful modeling, rats in the B4 group were intraperitoneally injected with anemoside B4(5 mg/kg), twice/day, for 8 weeks, while rats in the control and DM groups were injected with an equivalent volume of normal saline.After 8 weeks of anemoside B4 and normal saline injection, rats were sacrificed and retinas were harvested for examination.Paraffin sections of retina were stained with the hematoxylin-eosin(H-E)method for morphological evaluation.Protein levels of Bax and Bcl-2 were detected by using Western blot.The expression of caspase-3 mRNA was detected with quantitative PCR.Results:H-E staining results showed the control group had intact retinal structure and clear morphological features, whereas disordered retinal structure, thinner layers, and sparse and disorganized cells were seen in the DM group.However, retinal structure and morphology were improved after treatment with anemoside B4.Compared with the control group, the protein expression of Bcl-2 was lower( t=57.81, P<0.01), the protein expression of Bax was higher( t=10.47, P<0.01), and the Bcl-2/Bax ratio was lower( t=23.98, P<0.01)in the DM group.Compared with the DM group, the protein expression of Bcl-2 was higher( t=41.07, P<0.01), the protein expression of Bax was lower( t=6.811, P<0.01), and the Bcl-2/Bax ratio was higher( t=14.70, P<0.01)in the B4 group.Caspase-3 mRNA expression was higher in the DM group than in the control group( t=7.916, P<0.01), but was lower in the B4 group compared with the DM group( t=6.221, P<0.01). Conclusions:Anemoside B4 can inhibit the apoptosis of retinal cells by up-regulating Bcl-2 expression and down-regulating Bax and caspase-3 expression in diabetic rats.
Objective. To develop a method for the rapid isolation of rat RPE cells with high yield and maintain its epithelial state in modified culture system. Methods. The eyeballs were incubated with dispase. The retina was isolated with RPE attached and cut into several pieces. Following a brief incubation in growth medium, large RPE sheets can be harvested rapidly. RPE cells were divided into four groups and cultured for several weeks, that is, (1) in cell culture dishes with 10% FBS containing medium (CC dish-FBS), (2) in petri dishes with 10% FBS containing medium (Petri dish-FBS), (3) in cell culture dishes with N2 and B27 containing medium (CC dish-N2B27), and (4) in petri dishes with N2 and B27 containing medium (Petri dish-N2B27). Morphological and biological characteristics were investigated using light microscopy, Q-PCR, and western blot. Results. The retina would curl inwardly during the growth medium incubation period, releasing RPE sheets in the medium. Compared with low density group (5,000 cells/cm2), RPE cells plated at high density (15,000 cells/cm2) can maintain RPE morphology for a more extended period. Meanwhile, plating RPE cells at low density significantly reduced the expression of RPE cell type-specific genes (RPE65, CRALBP, and bestrophin) and increased the expression of EMT-related genes (N-cadherin, fibronectin, and α-SMA), in comparison with the samples from the high density group. The petri dish culture condition reduced cell adhesion and thus inhibited RPE cell proliferation. As compared with other culture conditions, RPE cells in the petri dish-N2B27 condition could maintain RPE phenotype with increased expression of RPE-specific genes and decreased expression of EMT-related genes. The AKT/mTOR pathway was also decreased in petri dish-N2B27 condition. Conclusion. The current study provided an alternative method for easy isolation of RPE cells with high yield and maintenance of its epithelial morphology in the petri dish-N2B27 condition.
Background Lipocalin-2 (LCN2) is a novel adipokine with potential roles in obesity, insulin resistance, and inflammation. This study aims to assess the concentrations of LCN2 and vascular endothelial growth factor (VEGF) expressed in the vitreous humors of patients with proliferative diabetic retinopathy (PDR). Methods The concentrations of LCN2 and VEGF were measured from the vitreous of 67 patients undergoing vitrectomy (20 controls and 47 PDR) via enzyme-linked immunosorbent assay (ELISA). Patients with non-ocular pathology that could elevate the LCN2 level in the vitreous were excluded. PDR activity and a history of panretinal photocoagulation were used for further grouping analysis. Results The vitreous concentration of LCN2 was statistically significantly higher in the PDR group compared to the control group (63,522 (30,009) pg/ml versus 1663 (1191) pg/ml, respectively; P < 0.001). VEGF level was also significantly higher in the PDR group than in the control group (1038 (1326) pg/ml versus 9 pg/ml, respectively; P < 0.001). The mean vitreous LCN2 and VEGF levels in active PDR patients were significantly higher than that of the inactive PDR patients. The mean LCN2 concentration in vitreous humor was significantly lower in the 28 PDR patients with a history of complete PRP (37,304 (16,651) pg/mL) in comparison with 19 PDR patients without preperformed panretinal photocoagulation or with preperformed incomplete panretinal photocoagulation (79,796 (24,391) pg/mL). A significant correlation between the vitreous LCN2 level and VEGF level was found in patients with PDR (R = 0.34; P = 0.019). Conclusions This report shows a significant increase of LCN2 in the vitreous fluid of patients with PDR and present a significant correlation between LCN2 and VEGF, suggesting LCN2 might be involved in the pathogenesis of PDR.
随着全国住院医师规范化培训(Standardized training of residents,简称“规培”)工作的深入开展,规培工作已成为培养现代高素质临床医师的必经之路.眼科属于外科但又不同于普通外科,眼球的精细结构及敏感功能决定了其手术的精细化及对术者的高要求.这就要求眼科医师在学习阶段就要打下良好的基础.但如何在短短3年时间内使进入规培基地的眼科住院医师掌握规范化的眼科显微手术技能,是摆在各规培基地领导及教师面前的重要课题.
Anti-VEGF based medicines have revolutionized the treatment paradigm for patients with ocular neovascularization and preserved the vision in most of the patients; this has become the first line therapy in the treatment of choroidal neovascularization (CNV). The decreased efficacy for anti-VEGF reagents was reported after multiple injections in certain patients for unknown reason, however no literature has reported the change of efficacy of the anti-VEGF therapy at early stages. Due to lack of a sensitive parameter to evaluate the efficacy of anti-VEGF reagents in the treatment of CNV, we developed a new method in this study, i.e., the reduction ratio of the maximum retinal thickness (MRT), to evaluate its efficacy. A retrospective, non-randomized study was analyzed in 30 eyes of 29 patients with CNV. The patients were intravitreally injected with either ranibizumab (12 eyes) or conbercept (18 eyes) for 2 consecutive injections at a 1-month interval. Best-corrected visual acuity (BCVA) was measured. Optical coherence tomography angiography (OCTA) was used for the measurement of the MRT, central retinal thickness (CRT), vessel density before and after injections. The reduction ratio of MRT and CRT was calculated and compared. After intravitreal injection, the BCVA was improved; MRT, CRT as well as vessel density was decreased. The trend was maintained but with less effect after the second injection. When compared with the reduction ratio of MRT of the first injection, the reduction ratio of MRT of the second injection was decreased significantly in both ranibizumab- and conbercept-treated groups. In conclusion, the reduction ratio of MRT was decreased after the second intravitreal injection of anti-VEGF reagents. The reduction ratio of MRT might be a sensitive parameter to evaluate the efficacy of anti-VEGF reagents in the treatment of CNV.
MicroRNAs (miRNAs) have been shown to play critical roles in the pathogenesis and progression of degenerative retinal diseases like age-related macular degeneration (AMD). In this study, we first demonstrated that miR-24 plays an important role in maintaining retinal structure and visual function of rats by targeting chitinase-3-like protein 1 (CHI3L1). In the retinal pigment epithelial (RPE) cells of Royal College of Surgeons (RCS) rats, an animal model of genetic retinal degeneration (RD), miR-24 was found lower and CHI3L1 level was higher in comparison with those in Sprague-Dawley (SD) rats. Other changes in the eyes of RCS rats include activated AKT/mTOR and ERK pathways and abnormal autophagy in the RPE cells. Such roles of miR-24 and CHI3L1 were further confirmed in RCS rats by subretinal injection of agomiR-24, which decreased CHI3L1 level and preserved retinal structure and function. Upstream, NF-κB was identified as the regulator of miR-24 in the RPE cells of these rats. On the other hand, in SD rats, intraocular treatment of antagomiR-24 induced pathological changes similar to those in RCS rats. The results revealed the protective roles for miR-24 to RPE cells and a mechanism for RD in RCS rats was proposed: extracellular stress stimuli first activate the NF-κB signaling pathway, which lowers miR-24 expression so that CHI3L1 increased. CHI3L1 sequentially results in aberrant autophagy and RPE dysfunction by activating AKT/mTOR and ERK pathways. Taken together, although the possibility, that the therapeutic effects in RCS rats are caused by other transcriptional changes regulated by miR-24, cannot be excluded, these findings indicate that miR-24 protects rat retina by targeting CHI3L1. Thus, miR-24 and CHI3L1 might be the targets for developing more effective therapy for degenerative retinal diseases like AMD.
Background Silicon oil tamponade eyes following vitrectomy accelerate and induce lens opacification,so the accurate measurement and calculation of intraocular lens (IOL) diopter before cataract extraction+ IOL implantation is very important for the recovery of visual function.Objective This study was to compare the differences of IOL powers measured and calculated by different apparatus and different IOL power formulas before cataract extraction + IOL implantation silicon oil tamponade combined with cataractous eyes.Methods A prospective,consecutive,nonrandomized study was performed.Thirty-six silicon oil tamponade with cataract eyes of 36 patients were included in the Second Affiliated Hospital of Soochow University from August 2011 to October 2013.Patients with silicone oil emulsification for 4 months to 2 years prepared to treat by cataract extraction + IOL implantation+silicon oil removal.Axial length (AL),corneal curvature (CC) and anterior chamber depth (ACD) were measured with IOLMaster and A-scan with manual kerameter (MK) in the eyes for the prediction of IOL power by SRK-Ⅱ,SRK/T,Hoffer Q,Holladay 1 and Haigis formulas under the oral informed consent.The mean predictive error (MPE) and mean absolute refractive error (MAE) between predictive IOL diopters before operation and actual IOL diopters after operation were evaluated.Results The AL and ACD values measured by IOLMaster was (25.43± 0.90)mm and (3.22±0.38)mm,which were significantly higher than (25.21±1.02)mm and (3.07±0.62) mm by A-scan+ MK respectively,the difference between the two measure methods was statistical significance (both at P =0.000).No significant difference was found in measured CC values between IOLMaster and A-scan+MK ([44.58±1.57] D vs.[44.56±1.62] D) (P=0.568).When the parameters measured by IOLMaster were used,the MAE from SRK/T formula was smaller than that from SRK-Ⅱ,Hoffer Q,Holladay 1 and Haigis formulas (P =0.017,0.009,0.012,0.001),and the MAE from Haigis formula was significantly larger than that from SRK-Ⅱ,Hoffer Q and Holladay 1 formulas (P =0.026,0.035,0.021).When measured by A-scan + MK,the MAE from Haigis formula was significantly larger than that from SRK-Ⅱ,SRK/T,Hoffer Q and Holladay 1 formulas (P=0.007,0.004,0.018,0.006).There was no significant difference in the number of eyes with MAE ≤ 1.0 D between IOLMaster and A-scan+MK measurements under the calculation of SRK-Ⅰ,SRK/T,Hoffer Q and Holladay 1 formulas (x2 =0.107,2.250,0.845,0.084,all at P>0.05).However,the number of eyes with MAE ≤ 1.0 D was significantly increased in IOLMaster measurement compared with A-scan+MK under the calculation of Haigis formula (x2 =4.431,P =0.035).Conclusions In silicon oil-filled cataract eyes,SRK/T formula appears to have a more accurate predictive value of IOL power than that of other formulas when employ IOLMaster;when use A-scan+MK measurement,the predictive value of IOL power seems to be better by using SRK-Ⅱ,SRK/T,Holladay 1 or Hoffer Q formulas.
Objective This study compared two methods for preparing retinal pigment epithelium (RPE) flat mounts and identified the difficulties of each method.The influences of each method on the RPE cell morphology and the integrity of RPE flat-mount were also presented.Methods In this experimental study,in the first method,direct flat mounts were prepared from rat eyes that were removed and fixed for 30 min in phosphate-buffered saline containing buffered 4% paraformaldehyde (PFA).The anterior segment of each eye and retina were removed.The remaining eye cup containing the RPE was radially cut into 4 to 6 pieces from the periphery to the optic nerve head.In the second method in which the RPE was isolated,the eye was removed and fixed as described above except that fixation continued overnight.For the isolated flat-mount technique,the anterior segments and retina were removed.The RPE-Bruch membrane complex was then carefully isolated from the remaining eye cup,and the upward facing RPE flat mount was formed by several relaxing radial cuts.Results The isolated flat-mount method could be used to obtain the whole RPE flat-mount,and the morphology of the RPE cells could be maintained.However,the preparation process of the direct flat-mount method could cause loss of the RPE cells,especially those at the edge of the sclera.Conclusion The direct RPE flat-mount method is simple and easy to perform except that the RPE cells at the edge of sclera are disrupted.The isolated RPE flat-mount method is relatively more difficult,but RPE cells are well preserved.
Background Fluoxetine (Flx),a selective serotonin reuptake inhibitor,promotes neurogenesis and synaptogenesis in the adult hippocampus.So it is inferred that Flx plays a role in promoting visual plasticity of visual cortex.However,the associations of oral administration of Flx with remodeling of visual plasticity and its difference from binocular form deprivation (BFD) are unelucidated.Objective This study was to investigate the influence of Flx application time to visual plasticity and contrast the mechanism between Flx and BFD in the remodeling of visual cortex plasticity in adult rats by pattern visual evoked potential (PVEP).Methods Fifty-six 70-day-old clean Wistar rats were randomized into control group,Flx2 group,Flx4 group,Flx6 group,Flx8 group,BFD group and Flx+BFD group.Flx was orally used at the dosage of 0.2 mg/ml once per day until 2,4,6 and 8 weeks before record of PVEP in the Flx2 group,Flx4 group,Flx6 group,Flx8 group respectively.The eyelids were binocularly sutured for 2 weeks and opened the right eyes 1 week before the record of PVEP to form the BFD and took the normal water in the rats of the BFD group,and the combination of Flx administration and BFD was performed in the Flx+BFD group.All the left eyes of the rats were sutured for 1 week to form the monocular form deprivation (MFD).No any intervene was conducted in the control group.PVEP was binocularly recorded in the rats to measure the amplitude from N75 wave to P100 wave,and amplitude ratio of left eyes and right eyes (C/I) was calculated.The results between before and after FD were compared to assess the shift of ocular dominance.The use and care of the animals followed ARVO Statement.Results The C/I of PVEP was significantly decreased 1 week after FD in comparison with before FD in the Flx4 group,Flx6 group,Flx8 group,BFD group and Flx+BFD group (t=2.733,P<0.05;t=2.981,P<0.05;t =3.619,P < 0.01;t =2.681,P < 0.05;t =4.550,P < 0.01).The amplitudes of PVEP were significantly lower in the left eyes after FD than those before FD in the Flx4 group ([17.71±2.24] μV vs.[31.09±4.13] μV),the Flx6 group ([18.93 ±2.85] μV vs.[29.59±4.07] μV) and the Flx8 group ([17.94± 1.92] μV vs.[28.48±3.09] μV)(t =3.348,3.278,4.447,all at P<0.01),while there were significant differences in the amplitudes of PVEP in the right eyes between before and after FD (all at P>0.05).The amplitudes of PVEP were reduced in the left eyes after FD in comparison with before FD in the BFD group and Flx4+BFD group (t=2.497,P<0.05;t=3.051,P<0.01),however,they were raised in the right eyes in both BFD group and Flx+BFD group (t=-4.009,P<0.01;t=-4.352,P<0.01).Conclusions Both 0.2 mg/ml Flx drinking for over 4 weeks and BFD for 2 weeks can restore visual cortex plasticity in the adult rats.Increasing the dosage time of Flx appears to be incapable to increase the remodeling degree of visual plasticity.Flx and BFD promote visual plasticity primarily by inhibiting the response of FD eyes and BFD can promote the response of non-FD eyes.Flx feeding and BFD play synergy effects in remodeling the visual cortex plasticity in adult rats.
Objective To make a summary of radiation-induced changes in ocular lens and retinal lesions based on dynamic follow-up of a patient exposed to a radiation exposure from 192 Ir source accident,in order to provide the information and experience for the clinical diagnosis and treatment of such injury in emergency of a nuclear or radiation accident.Methods The examination methods included eye lens and visual acuity,slit-lamp examination,fundus examination,automated perimetry,optical coherence tomography (OCT) examination,fundus photography,and fundus fluorescein angiography (FFA).The patient was followed-up for 20 months.Comparative analyses were made of the follow-up results.Results One month after 192Ir radiation exposure,the visual acuities in both eyes were 1.0.Mild age-related opacities were observed in peripheral cortex,but the fundus looked normal.Twenty months later,the patient was followed-up.The visual acuities reduced to about 0.6,evident powder-and punctuate-like opacities could be observed in the cortex of the right lens,and mild turbid foci in the posterior polar and capsule.Multiple scotomata appeared in the superior temporal and inferior nasal in the right eye.The macular fovea thickness was not changed significantly in the right eye.Examination with fundus photography demonstrated mild optical nerve atrophy,drusens,and pale optic discs,while FFA examination showed punctuate or flocculent leakages in both eyes.Conclusions The lens opacity could be induced or accelerated by radiation exposure.In addition to the posterior capsule and pole cataracts,punctuate opacity within cortical layer may also occur.It also suggests that cataract and fundus injuries may occur later during long-term follow-up,even though the eyes may look normal during early examination after the patient exposed to the radiation.
囊袋收缩综合征为白内障手术连续环形撕囊特有的并发症,引起术后视力下降等症状,残留的晶状体上皮细胞在囊袋收缩的发病机制中具有主导作用.通过合适撕囊、选择合适的人工晶状体、后囊膜抛光、Nd:YAG激光、手术切开囊膜等方法能有效的防治囊袋收缩综合征的发生.
PURPOSE Zinc transporter 8 (ZnT8) was downregulated in hypoxic retina, which could be rescued by hypoxia-inducible factor-1α (HIF-1α) inhibition. Erythropoietin (EPO) protects retinal cells in diabetic rats through inhibiting HIF-1α as one of its mechanisms. We hence tried to explore the effect of EPO in regulating ZnT8 and protecting retinal cells in diabetic rats and possible mechanisms. METHODS Diabetes was induced in Sprague-Dawley rats. Intravitreal injection of EPO was performed 1 month after diabetes onset. The CoCl2-treated rat Müller cell line (rMC-1) was cotreated with EPO, soluble EPO receptor (sEPOR), digoxin, or U0126. Cell viability, cell death, and intracellular zinc level were examined. The expression of ZnT8, HIF-1α, AKT, and ERK was studied. RESULTS In diabetic rat retinas, EPO significantly decreased HIF-1α expression and increased ZnT8 expression. In CoCl2-treated rMC-1 cells, EPO increased cell viability and decreased intracellular zinc. Erythropoietin or digoxin could activate ERK pathway, downregulate HIF-1α, and upregulate ZnT8. The effect of EPO was abolished by sEPOR and U0126. Transient knockdown of ZnT8 increased intracellular zinc level, but not to a degree that would decrease cell viability or cause cell death. CONCLUSIONS In diabetic retinas, EPO maintains zinc homeostasis through activating the ERK pathway and downregulating HIF-1α, and thus upregulating ZnT8 expression. This work proposed a possible new protective mechanism for EPO in, and indicated a potential target for, the treatment of diabetic retinopathy.
Objective To investigate the effects of multipotent adult progenitor cell (MAPC) conditions on biological characteristics and therapeutic effects of monkey bone marrow mesenchymal stem cells (BMMSCs) and human adipose-derived stem cells (hADSCs), thus to obtain optimal donor cells for treatment of retinal degeneration (RD). Methods The cell morphology, MTT assay, clone formation, adipogenic, osteogenic, chondrogenic differentiation potential and qRT-PCR technique were used to detect biological characteristics of monkey BMMSCs and hADSCs. The hADSCs were cultured under MAPC condition medium and transplanted into the subretinal space of RCS rats. The retinal functions were evaluated by electroretingram (ERG) recording, histological examination and TUNEL assay. Results Compared with conventional medium, MAPC conditions promoted the growth of monkey BMMSCs with smaller cell size. However, two passages later by subculture, monkey BMMSCs changed into larger and flatter morphology, showing senescence characteristics. MAPC culture conditions, compared with conventional hADSCs culture medium, maintained hADSC’s morphology, high proliferative capacity and multi-lineage differentiation potentials in long-term culture (beyond 10 passages), and fewer cells displayed senescence. Gene expression profiles for cell surface markers and cytokines showed a differential expression patterns:Under MAPC culture conditions, CD140b,CD90, CD47, HGF and PEDF were significantly up-regulated, whereas CD73, CD105 and IL-6 were significantly down-regulated compared with those under conventional culture medium. In comparison with untreated RCS rats, DMEM/LG-hADSCsand MAPC-hADSC transplanted RCS rats showed significantly improved b-wave amplitudes in ERG examination in 3 weeks after the transplantation, and significant reduction of apoptotic cells in the outer nuclear layer. Conclusions hADSCs treated with MAPC culture conditions were more effective in protect retinal neurons and hold great promise for clinical use in RD disease.