[Show abstract][Hide abstract] ABSTRACT: Neovascular glaucoma is a refractive glaucoma. Recently, anti-VEGF factors have been used alone or in combination for the treatment of neovascular glaucoma. However, the medium- and long-term efficacy of such drugs remains to be evaluated. This study was to determine the efficacy of intravitreal ranibizumab combined with Ahmed glaucoma valve implantation for the treatment of neovascular glaucoma.
In this prospective non-randomized study, 43 neovascular glaucoma patients (43 eyes) were assigned to receive either 0.5 mg intravitreal ranibizumab for three to 14 days before Ahmed glaucoma valve implantation (injection group, n = 21) or Ahmed glaucoma valve implantation alone (control group, n = 22). The patients were followed up for six to 12 months. Differences in surgical success rate, intraocular pressure, best corrected visual acuity, anti-glaucoma medications and postoperative complications were compared between the two groups. Surgical success was defined as IOP > = 6 mm Hg and < = 21 mm Hg, with or without the use of anti-glaucoma medications, and without severe complications or reoperation.
Of the 43 patients, 40 completed the 6-month follow-up and 37 completed the 1-year follow-up. Success rate was 73.7 % vs. 71.4 % at six months and 72.2 % vs. 68.4 % at 12 months in the injection group and the control group respectively. No significant difference was noted between the two groups (six months: P = 0.87, 12 months: P = 1.00). There were no significant differences in the two groups with respect to intraocular pressure, best corrected visual acuity, anti-glaucoma medications or postoperative complications at six months or 12 months.
Single intravitreal ranibizumab (0.5 mg) before surgery has no significant effect on the medium- or long-term outcomes of neovascular glaucoma treated with Ahmed glaucoma valve implantation.
Chinese Clinical Trial Registry (ChiCTR-OOC-14005709, Trial registration date: 2014-12-01)
[Show abstract][Hide abstract] ABSTRACT: Our previous studies suggest a critical role of Reticulon-1A (RTN1A) in mediating endoplasmic reticulum (ER) stress in kidney cells of animal models and human with kidney diseases. A large body of evidence suggests that proteinuria itself can cause tubular cell injury leading to the progression of kidney disease. Here, we determined whether RTN1A mediates proteinuria-induced tubular cell injury through increased ER stress. We found that the incubation of HK2 cells with human serum albumin (HAS) induced the expression of RTN1A and ER stress markers, while knockdown of RTN1A expression attenuated HAS-induced ER stress and tubular cell apoptosis in vitro. In vivo, we found that the tubular cell-specific RTN1 knockdown resulted in significant attenuation of tubular cell ER stress, apoptosis, and renal fibrosis in a model of albumin-overload nephropathy. Based on these findings, we conclude that RTN1A is a key mediator for proteinuria-induced tubular cell toxicity and renal fibrosis.
Preview · Article · Jan 2016 · AJP Renal Physiology
[Show abstract][Hide abstract] ABSTRACT: Background:
The reticulon 1 gene (RTN1) encodes reticulons, endoplasmic reticulum stress proteins recently implicated in kidney disease progression.
RTN1 single nucleotide polymorphisms (SNPs) were tested for association with type 2 diabetes (T2D)-associated end-stage kidney disease (ESKD) in African Americans (AAs) and European Americans (EAs), and AAs with non-diabetic ESKD. RTN1 SNPs that were associated with T2D-ESKD in AA cases compared to non-nephropathy controls were identified from a discovery genome-wide association study (n = 1,797), then tested for replication in 1,847 additional AA T2D-ESKD cases and controls.
Three intronic RTN1 variants were nominally associated with T2D-ESKD in both discovery and replication analyses: rs1952034, rs12431381 and rs12434215 (additive models); combined T2D-ESKD (discovery + replication) p values were 0.015-3.0 × 10-4 (ORs 0.67-0.77; minor alleles protective). In addition, rs12434215 was weakly associated with T2D-ESKD in 557 EA T2D-ESKD cases contrasted with 753 EA non-nephropathy controls (p = 0.019; OR 0.69, dominant model). Nominal association extended to non-diabetic causes of ESKD in 1,459 additional AA cases (rs12431381 and rs12434215 p values 0.014-0.015; OR 0.77). An all-cause ESKD association analysis contrasted the 3,594 AA ESKD cases with 1,489 AA non-nephropathy controls and detected association with rs12434215 (p = 6.7 × 10-4, OR 0.73) and rs12431381 (p = 7.5 × 10-4, OR 0.75) in dominant models. Of the 3 SNPs, only rs12434215 was weakly associated with T2D per se when contrasting T2D non-nephropathy cases with non-diabetic controls (additive model p = 0.032 AAs; p = 0.048 EAs).
These results suggest evidence of genetic association between common variants in RTN1 and ESKD in AAs and EAs.
No preview · Article · Oct 2015 · American Journal of Nephrology
[Show abstract][Hide abstract] ABSTRACT: Recently it was suggested that high myopia macular holes (HMMH) and macular holes accompanied by retinal detachment occur in the advanced stages of myopia traction maculopathy (MTM), while macular retinoschisis, shallow retinal detachment without holes, and lamellar macular holes occur in the early stages of MTM. Complete vitreous cortex removal associated with internal limiting membrane peeling is now widely used to treat HMMH. However, it remains uncertain at what HMMH stage patients would benefit most from surgical intervention. Our study was aimed to evaluate the postoperative anatomical changes and functional outcomes of high myopia macular holes (HMMH).
Patients were retrospectively collected between March 2009 and August 2011. Before and 1st, 3rd, and 9th month after 23G pars plana vitrectomy, all patients underwent a complete ophthalmologic examination, spectral domain optical coherence tomography (SD-OCT) and MP-1. At each follow-up, best-corrected visual acuity (BCVA), photoreceptor inner and outer segments (IS/OS) defects, and retinal sensitivity (RS) were investigated. According to different preoperative macular hole morphologies, patients were divided into three groups: Group 1, macular hole with epiretinal membrane (ERM) traction and macular retinoschisis; Group 2, full-thickness macular hole (FTMH); Group 3, FTMH with subretinal fluid.
43 eyes from 43 patients met the inclusion criteria. The mean age was 60 years. BCVA and RS were significantly improved after vitrectomy; the mean IS/OS defect was significantly reduced. At 9 postoperative months, 11 of 43 (25.6 %) eyes achieved IS/OS junction integrity; 9 of these 11 (81.8 %) eyes belonged to Group 1, 2 (18.2 %) belonged to Group 2.
Pars plana vitrectomy combined with ILM peeling and gas tamponade results in limited functional outcomes in patients with HMMH. The appearance of subretinal fluid indicates a worse prognosis for surgical intervention.
[Show abstract][Hide abstract] ABSTRACT: Identification of new biomarkers and drug targets for chronic kidney disease (CKD) is required for the development of more effective therapy. Here we report an association between expression of reticulon 1 (RTN1) and severity of CKD. An isoform-specific increase in the expression of RTN1A is detected in the diseased kidneys from mice and humans, and correlates inversely with renal function in patients with diabetic nephropathy. RTN1 over-expression in renal cells induces ER stress and apoptosis, whereas RTN1 knockdown attenuates tunicamycin-induced and hyperglycaemia-induced ER stress and apoptosis. RTN1A interacts with PERK through its N-terminal and C-terminal domains, and mutation of these domains prevents this effect on ER stress. Knockdown of Rtn1a expression in vivo attenuates ER stress and renal fibrosis in mice with unilateral ureteral obstruction, and also attenuates ER stress, proteinuria, glomerular hypertrophy and mesangial expansion in diabetic mice. Together, these data indicate that RTN1A contributes to progression of kidney disease by inducing ER stress.
[Show abstract][Hide abstract] ABSTRACT: Homeodomain interacting protein kinase 2 (HIPK2) functions as either a co-repressor or a co-activator of transcriptional regulators. Dysregulation of HIPK2 is associated with cancer and neurological disease. Recently, we found that HIPK2 is also an important driver of kidney fibrosis in the HIV-1 transgenic murine model, Tg26. HIPK2 protein levels are upregulated in the tubular epithelial cells of Tg26 mice as well as in kidney biopsies of patients with HIV-associated nephropathy, focal segmental glomerulosclerosis, diabetic nephropathy, and IgA nephropathy. We found that HIPK2 regulates pro-apoptotic, pro-fibrotic, and pro-inflammatory pathways including p53, transforming growth factor p (TGF-beta)-SMAD family member 3 (Smad3), Notch, Wingless and INT-1 (Wnt)/beta-catenin, and nuclear factor kappa-light-chain-enhancer of activated B cells in renal tubular epithelial cells. Our data suggest that HIPK2 may be a potential target for antifibrotic therapy. As mice with germline deletion of HIPK2 do not exhibit any phenotypic change under basal conditions, we do not expect significant side effects with specific HIPK2 inhibitors. However, potential effects of HIPK2 on tumor growth should be considered because of its tumor suppressor effects. Therefore, further understanding of structure-function relationships and post-translational modifications of HIPK2 are necessary to develop more specific drugs targeting the pro-fibrotic effects of HIPK2.
Full-text · Article · Nov 2014 · Kidney International Supplements
[Show abstract][Hide abstract] ABSTRACT: Diabetic retinopathy (DR) is a common complication of diabetes. DR obstructs blood supply to the retina and has serious and long-lasting detrimental effects on quality of life. Panretinal photocoagulation, a laser surgical intervention, is advocated for early treatment of DR to prevent visual loss; however, results from studies reporting its efficacy vary markedly. In this review, we systematically conducted a database search of randomized controlled trials that investigated the safety and efficacy of different types of laser interventions, alone or in combination with adjunct intravitreal steroid utilization, in patients with DR. Data from 14 studies demonstrated that panretinal photocoagulation can be a safe and effective option for reducing visual loss and blindness in patients with DR.
No preview · Article · Aug 2014 · Expert Review of Medical Devices
[Show abstract][Hide abstract] ABSTRACT: Profiling of temporal changes of gene expression in the same kidney over the course of renal disease progression is challenging because repeat renal biopsies are rarely indicated in clinical practice. Here, we profiled the temporal change in renal transcriptome of HIV-1 transgenic mice (Tg26), an animal model for human HIV-associated nephropathy (HIVAN), and their littermates at three different time points (4, 8, and 12 weeks of age) representing early, middle, and late stages of renal disease by serial kidney biopsy. We analyzed both static levels of gene expression at three stages of disease and dynamic changes in gene expression between different stages. Analysis of static and dynamic changes in gene expression revealed that up-regulated genes at the early and middle stages are mostly involved in immune response and inflammation, whereas down-regulated genes mostly related to fatty acid and retinoid metabolisms. We validated the expression of a selected panel of genes that are up-regulated at the early stage (CCL2, CCL5, CXCL11, Ubd, Anxa1, and Spon1) by real-time PCR. Among these up-regulated genes, Spon1, which is a previously identified candidate gene for hypertension, was found to be up-regulated in kidney of human with diabetic nephropathy. Immunostaining of human biopsy samples demonstrated that protein expression of Spon1 was also markedly increased in kidneys of patients with both early and late HIVAN and diabetic nephropathy. Our studies suggest that analysis of both static and dynamic changes of gene expression profiles in disease progression avails another layer of information that could be utilized to gain a more comprehensive understanding of disease progression and identify potential biomarkers and drug targets.
[Show abstract][Hide abstract] ABSTRACT: Background and aims:
The present study was designed to characterize and compare the ambulatory blood pressure changes of patients with Type 2 diabetic nephropathy (DN) and non-diabetic chronic kidney disease (CKD), and to investigate the features of ambulatory blood pressure in patients with Type 2 diabetic nephropathy (DN) in comparison with those of non-diabetic chronic kidney disease (CKD) in our medical center.
Materials and methods:
62 patients with Type 2 diabetic nephropathy (DN) in compliance with the diagnosis criteria of CKD were enrolled in the study, without renal replacement therapy. Their 24-h ambulatory blood pressure monitoring (ABPM) results were observed and compared with the ambulatory blood pressure results of 152 non-diabetic CKD patients with matching age, sex, renal function and other aspects.
Analysis of ABPM data from 62 patients with Type 2 DN and 152 patients with nondiabetic CKD indicated: 1. The average 24-h systolic blood pressure (SBP), daytime and nighttime systolic blood pressure (SBP) in the patients with DN were all significantly higher than those of patients with non-DN. 2. Blood pressure variability did not differ considerably between the two groups; nighttime blood pressure decline was small in both groups, but not significantly different. 3. The systolic blood pressure loads in the patients with DN were all significantly higher than those of patients with non-DN. 4. The prevalence of abnormal Circadian BP rhythm was 90.3% in patients with DN, which did not differ considerably from the patients with non-DN represented by 81.6%. 5. The nighttime SBP was correlated with 24-h urinary protein in patients with both non-DN and DN.
Systolic blood pressure control of patients with intermediate or advanced diabetic nephropathy was worse than that of patients with non-diabetic CKD, and non-dipping rhythm was quite common. The nighttime SBP correlated with 24-h urinary protein excretion.
No preview · Article · Oct 2012 · Clinical nephrology
[Show abstract][Hide abstract] ABSTRACT: Podocyte specific proteins are dysregulated in diabetic nephropathy, though the extent of their expression loss is not identical and may be subject to different regulatory factors. Quantifying the degree of loss may help identify the most useful protein to use as an early biomarker of diabetic nephropathy.
Protein expression of synaptopodin, podocin and nephrin were quantified in 15 Type 2 diabetic renal biopsies and 12 control patients. We found statistically significant downregulation of synaptopodin (P<0.0001), podocin (P = 0.0002), and nephrin (P<0.0001) in kidney biopsies of diabetic nephropathy as compared with controls. Urinary nephrin levels (nephrinuria) were then measured in 66 patients with Type 2 diabetes and 10 healthy controls by an enzyme-linked immunosorbent assay (Exocell, Philadelphia, PA). When divided into groups according to normo-, micro-, and macroalbuminuria, nephrinuria was found to be present in 100% of diabetic patients with micro- and macroalbuminuria, as well as 54% of patients with normoalbuminuria. Nephrinuria also correlated significantly with albuminuria (rho = 0.89, p<0.001), systolic blood pressure (rho = 0.32, p = 0.007), and correlated negatively with serum albumin (rho = -0.48, p<0.0001) and eGFR (rho = -0.33, p = 0.005).
These data suggest that key podocyte-specific protein expressions are significantly and differentially downregulated in diabetic nephropathy. The finding that nephrinuria is observed in a majority of these normoalbuminuric patients demonstrates that it may precede microalbuminuria. If further research confirms nephrinuria to be a biomarker of pre-clinical diabetic nephropathy, it would shed light on podocyte metabolism in disease, and raise the possibility of new and earlier therapeutic targets.
[Show abstract][Hide abstract] ABSTRACT: The accumulation of advanced glycated end products (AGEs) in retinal blood vessels is one of the major etiological factors contributing to diabetic retinopathy. Aminoguanidine (AG) is one of the most extensively used inhibitors of AGEs formation. The aim of this study was to investigate whether AG could protect the development of diabetic retinopathy through inhibition of AGEs.
Rat diabetes was induced by intraperitoneal injection with streptozotocin (STZ). AG was given to rats in drinking water. Retina was extracted 3 and 6 months following STZ and AG administration. Immunochemistry and transmission electron microscope were used to detect the expression of AGEs and retina morphology.
Extensive staining of AGEs was detected in retinal blood vessels of 3- and 6-month diabetic rats, while no significant staining was found in the control non-diabetic retina or AG treated groups. Pericyte loss, endothelial cell proliferation, increased ratio of endothelial cells/pericytes, acellular capillaries and capillary occlusion were observed in the retina of 6-month diabetic rats. The increased electron density of retinal capillary basement membrane, mitochondrial swelling in pericytes and endothelial cells were also found in 6-month diabetic rats. The 3-month diabetic rats and the AG-treated rats did not have similar morphological changes compared to control group. The AGEs staining in AG-treated rats was still weakly positive.
AGEs plays pivotal roles in diabetic retinopathy. AGE deposition occurs prior to retinal microvasculature changes. AG could prevent the onset and development of diabetic retinopathy through inhibition of AGEs.
No preview · Article · May 2012 · Bioorganic & medicinal chemistry letters
[Show abstract][Hide abstract] ABSTRACT: Kidney fibrosis is a common process that leads to the progression of various types of kidney disease. We used an integrated computational and experimental systems biology approach to identify protein kinases that regulate gene expression changes in the kidneys of human immunodeficiency virus (HIV) transgenic mice (Tg26 mice), which have both tubulointerstitial fibrosis and glomerulosclerosis. We identified homeo-domain interacting protein kinase 2 (HIPK2) as a key regulator of kidney fibrosis. HIPK2 was upregulated in the kidneys of Tg26 mice and in those of patients with various kidney diseases. HIV infection increased the protein concentrations of HIPK2 by promoting oxidative stress, which inhibited the seven in absentia homolog 1 (SIAH1)-mediated proteasomal degradation of HIPK2. HIPK2 induced apoptosis and the expression of epithelial-to-mesenchymal transition markers in kidney epithelial cells by activating the p53, transforming growth factor β (TGF-β)-SMAD family member 3 (Smad3) and Wnt-Notch pathways. Knockout of HIPK2 improved renal function and attenuated proteinuria and kidney fibrosis in Tg26 mice, as well as in other murine models of kidney fibrosis. We therefore conclude that HIPK2 is a potential target for anti-fibrosis therapy.
[Show abstract][Hide abstract] ABSTRACT: To identify the correlation between serum-based differentially expressed proteins and pathological myopia.
It was a case-control study. The serum of 30 pathological myopia patients and 30 age- and gender-matched normal controls were collected from Shanghai First People's Hospital affiliated to Shanghai Jiaotong University. These patients were divided into 4 groups including macular-off retinal detachment (8 cases), retinal geographic atrophy (5 cases), macular hole (11 cases) and choroidal neovascular (6 cases). The serum specimens of normal controls were used as immunogen to immune rabbits in order to prepare polyclonal antibodies. Purified by Protein A cartridge, these mixed antibodies were then combined with CNBr-activated Sepharose so as to synthesize affinity medium which was finally used to treat the serum specimens. According to the theory of antigen and antibody, common background proteins would be deleted. The remaining non-binding proteins were analyzed by capillary high-performance liquid chromatography and LTQ-MASS. Nonparametric statistical analysis was used to detect the correlation each differentially expressed protein.
The result of HPLC and LTQ-MASS in 30 specimens of patients revealed 4 peaks of differentially expressed proteins including JTR (positive in 18 specimens, 60%), HP( positive in 11 specimens, 36.7%), HPX (positive in 10 specimens, 33.3%), APO (positive in 8 specimens, 26.7%). There were positive correlations between these 4 proteins (the correlation between TTR and HP, HPX, APO is r = 0.480, 0.577, 0.492; the correlation between HP and TTR, HPX, APO is r = 0.480, 0.783, 0.636; the correlation between HPX and TTR, HP, APO is r = 0.577, 0.783, 0.853; the correlation between APO and TTR, HP, HPX is r = 0.492, 0.636, 0.853; P < 0.05). In group of macular hole, TTR was positive expressed in 7 specimens while other differential proteins were low expression. In group of choroidal neovascular, TTR and HP were positive expressed in 6 specimens while HPX was significantly high in 5 specimens. In other two groups, the expression of 4 differential proteins was rather low.
Screening molecular biomarkers by serum-based proteomics can efficiently exclude common proteins and find differential proteins correlated with pathological myopia. These differential proteins may become molecular biomarks of pathological myopia in the future.
No preview · Article · Mar 2012 · [Zhonghua yan ke za zhi] Chinese journal of ophthalmology
[Show abstract][Hide abstract] ABSTRACT: Recent studies have revealed that melatonin exerts strong anti-apoptotic effects. Retina secretes melatonin, and melatonin receptors are distributed in almost all the layers of retina, including the layer of retinal pigment epithelial (RPE) cells. However, it is not known whether melatonin inhibits apoptosis through its anti-oxidant effects and how it works in RPE cells. Here, we show that melatonin decreases H2O2-induced apoptosis in RPE cells partially through protection of mitochondria. Melatonin decreased reactive oxygen species in mitochondria and mitochondrial DNA damage, alleviated structural damage and inhibited cytochrome C release.
No preview · Article · Jan 2012 · Frontiers in Bioscience
[Show abstract][Hide abstract] ABSTRACT: to analyze the efficacy of low-energy selective laser trabeculoplasty (SLT) in patients.
in 74 patients (74 eyes) with ocular hypertension, suspected glaucoma, or primary open-angle glaucoma, SLT was the first-choice treatment. Thirty-nine patients in the low-energy group received treatment using half of conventional laser energy over 360° of the trabecular meshwork (at 100 points). Thirty-five patients in the control group received conventional laser energy. Patients were observed for 1 year. Complications and intraocular pressure (IOP) were observed.
postoperative transient IOP spike (≥ 3 mm Hg) occurred in three eyes on the day of treatment and partial peripheral anterior synechiae occurred in one eye 1 month after treatment only in the control group. Effective rates of treatment (≥ 20% IOP reduction) at week 2 and month 1, 3, 6, and 12 after treatment were 69.23%, 64.10%, 61.54%, 53.85%, and 48.72% in the low-energy group and 71.43%, 71.43%, 60%, 51.43%, and 48.57% in the control group, respectively. There was no statistically significant difference between the two groups at various time points (P = .836, .501, .892, .835, .990).
compared with SLT using conventional laser energy, low-energy SLT lowers IOP with fewer complications, making it a safe and effective option.
No preview · Article · Oct 2011 · Ophthalmic Surgery Lasers and Imaging
[Show abstract][Hide abstract] ABSTRACT: To detect serum and vitreous transthyretin (TTR) in high myopia patients and to evaluate potential associations between TTR and clinical parameters and ocular pathologies, including different ocular pathologies.
Serum samples from 16 high myopia patients and 4 controls were analyzed by LTQ-MASS. Serum samples from 116 high myopia patients and 86 healthy controls were tested by Western blots and ELISA. Eight healthy and 40 pathologic vitreous samples were analyzed by ELISA. And corresponding serum samples were also analyzed by ELISA.
Significant increased TTR serum levels were detected in high myopia patients compared to healthy controls. The high levels of serum TTR were associated with ocular pathologies, long axial length, and low visual acuity. TTR in high myopia patients with macular hole and macular detachment was upregulated in both vitreous and the corresponding serum samples. TTR levels in serum samples of high myopia patients with long axial lengths were higher than in the vitreous.
Serum TTR may be a biomarker for high myopia patients with ocular pathologies.
No preview · Article · Mar 2011 · Clinical biochemistry
[Show abstract][Hide abstract] ABSTRACT: To explore the value of color Doppler ultrasound in evaluating the therapeutic effects on ankylosing spondylitis (AS) patients.
Color Doppler high-frequency ultrasound images and blood flow in 30 healthy volunteers and 50 AS patients, changes of high-frequency ultrasound images and blood flow of involved sites in AS patients pre- and after-Etanercept treatments, as well as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and the Bath AS disease activity indices pre- and post-treatment were compared.
Positive rates were significantly different between healthy volunteers and AS patients in terms of sacroiliac joints, Achilles tendon attachments, patellar ligament attachments, and rectus femoris tendon attachments by ultrasonograph (P < 0.05); and the fibular collateral ligament attachments positive rates had no significant difference with those at pre-treatment (P > 0.05). There was significant difference between patients with Bath AS disease activity index (BASDAI) ≥ 4 and those with BASDAI < 4 with respects to peripheral enthesis positive rate, Bath AS functional index (BASFI), patient's global assessment VAS (PGA), nocturnal back pain and general back pain VAS, morning stiffness duration, ESR and CRP (P < 0.05). Positive rates of sacroiliac joints, Achilles tendon attachments, patellar ligament attachments and rectus femoris tendon by ultrasonograph significantly decreased at Weeks 12 and 24 at post-treatment compared to that at pre-treatment (P < 0.05); there was significant difference for patient's BASDAI, BASFI, ESR and CRP at pre-treatment and weeks 12 and 24 post-treatment (P < 0.05).
Ultrasound can sensitively detect the pathological changes of joint synovium and entheses so that it may be used as a routine method of monitoring diseases in these soft tissues, following up AS patients and evaluating clinical efficacy.
No preview · Article · Jul 2010 · Zhonghua yi xue za zhi
[Show abstract][Hide abstract] ABSTRACT: This study was designed to investigate whether synthetic small interference RNA (siRNA) targeting VEGF-A could inhibit mouse corneal neovascularization or not.
First, the effect of synthetic siRNA targeting VEGF-A on the expression of VEGF in human retinal pigment epithelial line ARPE-19 cells was examined. Corneal neovascularization was induced on the right cornea of C57BL/6 mice by alkali burn. Mice were randomly divided into 4 groups (21 animals in each group): VEGF-A siRNA group, stable negative siRNA group, saline control group, and blank control group. After alkali burn, except for the blank control group, the other 3 groups were subconjunctivally injected with VEGF-A siRNA, stable negative siRNA, and normal saline, respectively. On days 3 and 7 after alkali burn, the concentration of VEGF in the cornea was determined by ELISA kit. On day 10, the neovascularized corneal area was mensurated, the amount of corneal new vessels was quantified by CD31 immunohistochemical assay of corneal sections, and permeability of new vessels was shown by fluorescence angiography.
After comparing the histological appearance of the cornea between the VGF-A siRNA group and the 3 control groups on days 10 and 30, it was found that in the VEGF-A siRNA group, not only was VEGF expression in the cornea induced by alkali burn but also neovascularized corneal area and amount of new vessels were reduced, followed by the permeability of new vessels, and corneal histological structure were improved. It was also found that the exposure to VEGF-A siRNA significantly reduced the VEGF-A mRNA expression in AREP-19 cells. These findings suggested synthetic siRNA targeting VEGF-A delivered by subconjunctival injection could inhibit corneal angiogenesis induced by alkali burn.
VEGF-A siRNA could potentially serve as an important therapeutic alternative in the management against unwanted angiogenesis including corneal neovascularization.
No preview · Article · May 2010 · Current eye research