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Objective To analyze the BEST1 gene mutations and clinical features in patients with multifocal vitelliform retinopathy (MVR).Methods This is a retrospective case series study.Five MVR families with MVR,including 9 patients and 10 healthy family members were recruited.Clinical evaluations were performed in all MVR patients and their family members,including best-corrected visual acuity (BCVA),intraocular pressure (IOP),refraction,slit-lamp examination,90 D preset lens examination,gonioscopy,color fundus photography,optical coherence tomography (OCT),fundus autofluorescence (AF),ultrasound biomicroscopy (UBM) and axial length measurement.Electro-oculogram (EOG) was performed in 12 eyes and visual field were performed in 13 eyes.Peripheral blood samples were collected in all subjects to extract genomic DNA.Coding exons and flanking intronic regions of BEST 1 were amplified by polymerase chain reaction and analyzed by Sanger sequencing.Results Among the 5 MVR families,3 probands from three families had family history,including 1 family had autosomal dominant inheritance pattern.Two patients from 2 families were sporadic cases.Screening of BEST1 gene identified four mutations,including three missense mutations (c.140G＞T,p.R47L;c.232A＞T,p.I78F;c.698C＞T,p.P233L) and 1 deletion mutation (c.910_912del,p.D304del).Two mutations (p.R47L and p.I78F) were novel.The BCVA of affected eyes ranged from hand motion to 1.0.The mean IOP was (30.39± 11.86) mmHg (1 mmHg=0.133 kPa).The mean refractive diopter was (-0.33 ± 1.68) D.Twelve eyes had angle-closure glaucoma (ACG) and 4 eyes had angle closure (AC).EOG Arden ratio was below 1.55 in all patients.The mean anterior chamber depth was (2.17± 0.29) mm.Visual field showed defects varied from paracentral scotoma to diffuse defects.The mean axial length was (21.87± 0.63) mm.All MVR patients had multifocal vitelliform lesions in the posterior poles of retina.ACG eyes demonstrated pale optic disc with increased cup-to-disc ratio.OCT showed retinal edema,extensive serous retinal detachment and subretinal hyper-reflective deposits which had high autofluorescence in AF.The genetic testing and clinical examination were normal in 10 family members.Conclusions MVR patients harbored heterozygous mutation in the BEST1 gene.Two novel mutations (p.R47L and p.I78F) were identified.These patients had clinical features of multifocal vitelliform retinopathy and abnormal EOG.Most patients suffered from AC/ACG.
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[Objective]The oxidative injury of retinal pigment epithelium(RPE)plays a key role in the pathogenesis of age-related macular degeneration(ARMD). This study is to investigate the effects of endoplasmic reticulum stress and the vital transcriptional factor X-box binding protein 1(XBP1)in acrolein-induced oxidative damage of RPE.[Methods]RPE cells were treated with acrolein (75μmol/L)for 2~24 h,expression of glucose regulated protein 78(GRP78)and XBP1 was determined by Western blot analysis. After being transfected with XBP1 siRNA with 24 h,the expression of XBP1 was knocked-down in RPE cells. Protein level of Nrf2 and SOD2 was then determined by Western blot analysis and intracellular Reactive Oxygen Species(ROS)generation was determined by DCF staining. Acrolein was added for 8 h after being transfected with XBP1 siRNA or control siRNA for 24 h. Apoptosis was detected by TUNEL assay before and after the treatment. Subretinal injection of Cre or GFP adenovirus was performed in XBP 1flox mice. After 1 week the mice were sacrificed. Total RNA was extracted from mice eyecups using TRIzol and real-time RT-PCR was performed to determine the two XBP1 down-stream genes,ERdj4 and p58IPK. Cryosectioning and immunofluorescent staining were performed to look at the expression of XBP1,Nrf2 and SOD2 in mice RPE.[Results]Protein level of GRP78 was significantly un-regulated after exposure to acrolein for 2 and 4 h. XBP1 was activated after acrolein treatment for 6 h. Knock-down of XBP1 by siRNA down-regu?lates anti-oxidant genes expression and increased ROS generation in RPE cells. Loss of XBP1 exacerbates acrolein-induced cell apoptosis. XBP1 was knocked-down in the RPE of XBP1flox mice after subretinal injection of Cre adenovirus. Decreased mRNA level of ERdj4 and p58IPK,and decreased Nrf2 and SOD2 expression were seen in the Cre-injected group.[Conclusions]Acrolein induces ER stress and activates XBP1 in RPE cells. Knock-down of XBP1 down-regulates anti-oxidant genes expression ,increases ROS generation,and exacerbates acrolein-induced cell apoptosis. XBP1 plays a role in the anti-oxidant defense in the RPE cells.
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Objective To investigate the effect of trabeculectomy combined with segmental iridectomy, mitomycin C (MMC) and viscoelastic agents usage on the treatment of glaucoma secondary in uveitis. Methods According to the age, degree of inflammation and the condition of Tenon capsule of patients, differ-ent concentration of MMC (0.25-0.33 mg/ml) was used during the operation, with separation of the anterior and posterior synechia, resection of pupillary organization membrane using viscoelastic agents. Segmental iridec-tomy and releasable sutures were also performed on the patients. The visual acuity of preoperation and postoper-ation, intraocular pressure, inflammation and the complication were record. Results Forty-two eyes of 38 cases with glaucoma secondary in uveitis were studied, the mean follow-up time was (12.01±3.56) months. The postoperative visual acuity improved in 14 eyes, didn't change in 28 eyes. The postoperative inflammation of anterior chamber disappeared in 35 eyes, relieved in 7 eyes. And the average postoperative intraocular pres-sure (15.20± 4.64) mmHg was significantly lower than the preoperative intraocular pressure (38.37±12.93) mmHg (t = 8.255, P = 0.000). The total success rate was 92.9%. There were no severe complication. Conclusion Trabeculeetomy combined with MMC, viscoelastic agents usage, separation of anterior and poste-rior syneehia, segmental iridectomy and releasable suture could increase the success rate of operation on pa tients with glaucoma secondary in uveitis, decrease the complication and inflammation reaction of operation, and the recurrence of uveitis.
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Objective To investigate the early influence nf trabeculectomy on tear film and epithelial cells of ocular surface.Methods Twenty-six patients (36 eves) with glaucoma underwent trabeculectomy with adjustable suture,and with or without use of intraoperative mitomycin-C(MMC) undel conjunctiva and sclera were included from March 2006 to May 2007.Routine ocular examinations and ocular surface examina- tions,including Schirmer I test,break-up time,fluorescein staining,rose bengal staining,and conjunctival impression cytology,were conducted preoperatively and 1 month postoperatively.Results Compared with normal controls,troth postoperative and preoperative BUT were significantly shortened,and FL,RB scores, conjunctival Nelson classification significantly higher,and goblet cell density was significantly decreased in glaucomatous patients.No statistically significant difference of Sit were observed between the patients and the normal controls.There were no statistically significant difference of Sit,BUT,FL and RB scores between pre- operation and 1 month postoperation.Postoperative conjunctival Nelson classification was significantly higher than preoperative level,and goblet cell density was significantly lowered.There were no significant difference of Slt,BUT,Nelson classification and goblet cell density between 0.25 mg/ml MMC group and the control preoperatively and 1 month pnstoperatively.The FL and RB scores of the control group were significantly high- er than MMC group postoperatively.Conclusion There may be some influence of trabeculectomy on tear film stability and ocular surface epithelium,which is manifested by teat film unstability,epithelial staining, conjunctival squamous metaplasia,and goblet cell density decrease 1 month postoperatively.These may not be related to use of low concentration of MMC in operation.
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AIM:To evaluate the effects of pilocarpine, brinzolamide and the preservatives of them on corneal epithelial cells and the histopathology of rabbit conjunctiva. METHODS: Fifteen New Zealand white rabbits weighing 1.5 kg to 2.5 kg were randomly divided into three groups. One group with three rabbits served as untreated controls. Pilocarpine 1% and brinzolamide 1% each were administered to the right eyes in one treated group, and the preservatives (chlorobutanol 0.01% in pilocarpine, benzalkonium chloride 0.01% in brinzolamide) to the left eyes. Corneal epithelial damage was evaluated by scanning electron microscopy, and conjunctival specimens were examined under light microscopy. RESULTS: Compared with normal controls, brinzolamide and BAC caused corneal epithelium damage and increased number of inflammatory cells in the conjunctiva, while pilocarpine and the preservative chlorobutanol mainly influenced the corneal epithelium. Brinzolamide produced significantly more damage than pilocarpine (P