Bevacizumab vs ranibizumab for neovascular age-related macular degeneration in Chinese patients

AIM: To compare the clinical efficacy of intravitreal injections of bevacizumab and ranibizumab for treating Chinese patients with neovascular age-related macular degeneration (AMD).METHODS: Among 60 Chinese patients with exudative AMD (60 eyes), 28 received intravitreal bevacizumab injections (1.25mg) and 32 received intravitreal ranibizumab injections (0.5mg), once a month for 3 months and were followed for a total of 6 months. Monthly optical coherence tomography (OCT) was used to determine whether the patients received additional treatments during the follow-up. We compared the baseline and 6 -month follow-up values of mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in both groups of patients. We also compared the occurrence of adverse events.RESULTS: At the 6-month follow-up, the mean BCVA (logMAR) of the bevacizumab and ranibizumab treatment groups improved from the baseline measurements of 0.72 ±0.23 and 0.73 ±0.22 to 0.47 ±0.14 and 0.45 ±0.20, respectively (P 【0.05 for both groups). However, the change was not significantly different between the two groups. As evaluated by OCT, CRT decreased from 366.71 ±34.72μm and 352 ±36.9μm at baseline to 250.86 ± 41.51μm and 243.22 ±41.38μm in the bevacizumab and ranibizumab groups, respectively (P 【0.05 for both groups). However, the change was not significantly different between the two groups. There were no severe local adverse reactions or systemic adverse events.CONCLUSION:Intravitreal bevacizumab and ranibizumab have equivalent effects on BCVA and CRT and appeare safe over the short-term.

Comparison of visual acuity outcomes between ranibizumab and bevacizumab treatment in neovascular age-related macular degeneration

AIM: To compare visual acuity (VA) outcomes between intravitreal injection of bevacizumab and ranibizumab in the treatment of neovascular age-related macular degeneration (AMD). METHODS: We conducted a consecutive, retrospective case series study in patients with newly diagnosed all type choroidal neovascularization (CNV) secondary to AMD who received an intravitreal injection of bevacizumab (1.25mg) or ranibizumab (0.3mg) at Lions Eye Institute, Western Australia from Mar. 2006 to May 2008. All patients received injection at baseline with additional monthly injections given at the discretion of the treating physician. Main outcome measures were changes in VA. RESULTS: There were 371 consecutive patients received injection at least in one eye with at least 6 months of follow up (median of 12.0 months). Bevacizumab treatment prevented 221 out of 278 (79.5%) patient from losing < 15 letters in VA compared with 79 out of 93 (84.9%) of ranibizumab treated patients (P=0.25). While 68 (24.5%) of bevacizumab treated patients gained 15 letters of VA compared with 24 (25.8%) of ranibizumab treated patients (P=0.79). 75.3% and 66.2% patients benefited from ranibizumab and bevacizumab respectively with final VA better than 6/60 (P=0.10). Multivariate analysis showed that pre-treatment VA was negatively associated with benefit outcome. Assignment of injection was not associated with VA outcome of benefit after adjusting the covariate (P=0.857). CONCLUSION: There are no difference in treatment efficacy in terms of VA between bevacizumab and ranibizumab in routine clinical condition.

Effect of Quercetin on Formation of Choroidal Neovascularization (CNV) in Age-related Macular Degeneration (AMD)

Purpose:Age-related macular degeneration(AMD)as a disease entity is "dry" at early stage and made up of two main components at late stage:atrophic AMD and exudative AMD.Quercetin acts as an anti-oxidant to protect retinal pigment epithelial cells(RPE)from damaged by oxidative stress,but its effect on formation of choroidal neovascularization(CNV)in AMD is unclear.The aim of this study is to investigate the effect of quercetin on the formation of CNV in AMD.Methods:The development of CNV induced by laser was detected.by fluorescein angiography(FA).Colored microsphere technique was used to determine the choroidal blood flow in ocular hypertensive rabbit eyes.In in vitro studies,HUVECs were treated with NaIO3,H2O2 and NaN3 to induce oxidative cell damages.The effect of quercetin on various oxidations-induced injuries in HUVECs was measured by MTT assay.HUVECs migration was assessed using a wound healing assay.Results:Quercetin significantly inhibited the formation of laser-induced CNV.The choroidal blood flow in rabbit eyes was significantly increased after quercetin instillation.In vitro results showed quercetin enhanced various oxidations-induced injuries in HUVECs and inhibited migration of HUVECs during wound healing.Conclusion:Quercetin inhibited the formation of CNV both in vivo and in vitro and increased choroidal blood flow.It could become a promising candidate for the treatment of AMD.

Comparison of two different treatment regimens’ efficacy in neovascular age-related macular degeneration in Turkish population—based on real life data-Bosphorus RWE Study Group

AIM: To compare two different anti-vascular endothelial growth factor(anti-VEGF) treatment regimens'-a priori pro re nata(PRN) and PRN regimen following^(th)e loading phaseanatomical and functional results in neovascular agerelated macular degeneration(n AMD) patients. METHODS: Totally 544 n AMD patients followed and treated with aflibercept(n=135) and ranibizumab(n=409)at 9 different centers between 2013 and 2015 were enrolled into^(th)is retrospective multicenter study. Patients with initial best corrected visual acuity(BCVA) interval of 1.3-0.3(log MAR) and a minimum follow-up of 12 mo were included. Patients under two different regimens-a priori pro re nata(1+PRN) or 3 consecutive intravitreal injections followed by a PRN regimen(3+PRN)-were compared in BCVA at 3^(th), 6^(th) and 12^(th) months, and in central macular^(th)ickness(CMT) at 6^(th) and 12^(th) months. The total study group, intravitreal ranibizumab(IVR) and intravitreal aflibercept(IVA) groups were evaluated separately. RESULTS: The mean CMT decreased in^(th)e 1+PRN(n=101) regimen from 407 to 358 and 340 μm and in^(th)e 3+PRN(n=443) group from 398 to 318 and finally to 310 μm at months 6 and 12, respectively. Anatomically,^(th)e CMT reduction at 6^(th) month(48.5 vs 76.4;P<0.05) was statistically significant in favor of 3+PRN group. BCVA changed in 1+PRN group from 0.77 to 0.78, 0.75 and 0.75;in 3+PRN group from 0.81 to 0.69, 0.72, and 0.76 at months 3, 6, and 12, respectively. Visual gain was statistically better in 3+PRN group at 3^(th) month(-0.01 vs 0.12;P<0.001). In IVR group, CMT reduction was in greater in 3+PRN at 6^(th)(44 vs 72) and 12^(th) month(61 vs 84), but statistically insignificant. The 3+PRN group revealed statistically better visual results at 3^(th) month(-0.02 vs 0.11, P<0.05). In IVA group, although statistically insignificant, CMT reduction(61 vs 89, 6^(th) month;85 vs 97, 12^(th) month) and visual gain(0.02 vs 0.16;0.02 vs 0.14;0.05 vs 0.11) was found in favor of 3+PRN group at all visits.CONCLUSION: The loading dose of anti-VEGF treatments in n AMD leads to significantly better anatomical and functional results, regardless of the agent, specially in early follow-up interval.

Assessment of the long-term visual and anatomical outcomes of ranibizumab to treat neovascular age-related macular degeneration

AIM： To investigate the long-term visual and anatomical outcomes of patients who underwent intravitreal ranibizumab monotherapy to treat neovascular age-related macular degeneration（AMD） and followed-up for at least 2 y.METHODS： A total of 74 eyes of 74 patients who underwent ranibizumab monotherapy for neovascular AMD were included in this retrospective study.RESULTS： The average patient age was 72.1±6.5（range, 57-85）y, the average follow-up time 46.2±13.1（range, 24-75）mo, and the average number of visits 24.1±9.5（range, 8-48）. The mean number of injections in year 1 was 4.5, 1.6 in year 2, 0.9 in year 3, 0.4 on year 4, and 0.1 in the following years. Within the entire follow-up period, the mean number of injections was 7.6±4.4（range, 2-21）. The mean visual acuity was 48.1±15（range, 15-76） letters at baseline and 45.7±19（range, 7-75） at year 5. The mean central macular thickness was 303±78（range, 178-552） μm at baseline and 251±51（range, 138-359） μm at year 5. Scars developed in 47（63.5%） eyes at the end of the follow-up period, and atrophy was evident in 6（8.1%） eyes.CONCLUSION： Ranibizumab monotherapy can stabilize visual acuity for a mean period of 4 y in patients with neovascular AMD.

6-weekly bevacizumab versus 4-weekly ranibizumab for neovascular age-related macular degeneration:a 2-year outcome

AIM： To compare visual acuity and central macular thickness（CMT） changes in neovascular age-related macular degeneration patients treated with either 6weekly bevacizumab regimen or 4 weekly ranibizumab on an as required basis.·METHODS： Patients made an informed choice between bevacizumab 1.25 mg or ranibizumab 0.5 mg. The selected treatment was administered in the first 3 visits.Bevacizumab patients were followed-up 6 weekly and ranibizumab 4 weekly. Retreatment criteria was based on the reduction of 〉5 letters in the best-corrected visual acuity（BCVA）, the presence of retinal fluid on optical coherence tomography（OCT） or new retinal haemorrhage.·RESULTS： Visual acuity at 2y bevacizumab patients gained 7. 0 letters and ranibizumab 9. 2（ P = 0. 31, 95 %CI-6.4 to 2.0）. At 2y 86% of bevacizumab and 94%ranibizumab patients had not lost 15 letters or more（P =0.13）. Mean CMT decreased at 2y bevacizumab by 146 μm,ranibizumab 160 μm（P =0.72）. Mean number of injections was at 2y bevacizumzb 11.9, ranibizumab 10.3（P =0.023）.· CONCLUSION： Bevacizumab 6 weekly on an as required basis was not demonstrably non-inferior to ranibizumab 4 weekly pro re nata（prn） in terms of BCVA and change in CMT. In the bevacizumab group, one more injection was required in the second year compared to the ranibizumab group.

Bevacizumab versus ranibizumab for neovascular agerelated macular degeneration: a Meta-analysis

AIM: To systematically compare the efficacy and safety of off-label bevacizumab versus licensed ranibizumab intravitreal injections as well as monthly regimen versus pro re nata [PRN(as needed)] regimen in the treatment of neovascular age-related macular degeneration(n AMD).METHODS: Relevant publications were identified through automatically retrieve of database and manually retrieving. The methodological quality of studies included was assessed using the Jadad score and the risk-of-bias assessment. The efficacy estimates were measured by the weight mean difference(WMD) for the improvement of best-corrected visual acuity(BCVA) and central retinal thickness(CRT) reduction. The safety estimates were measured by odds ratios(OR) for adverse events rates. Statistical analysis was conducted by Revman 5.2.7.RESULTS: Seven studies were included in the Metaanalysis. There were no statistically significant differences between bevacizumab and ranibizumab in BCVA at 1 and 2y(P =0.37, P =0.18, respectively),However, both drugs has better BCVA given monthly than given as needed at 1 and 2y(P 【0.05). The results demonstrated the mean decrease in CRT was less in bevacizumab group than ranibizumab group at 1y(P 【0.05),while the difference was not significant at 2y(P =0.24).Treatment monthly gained much more decrease in CRT at 1 and 2y(P 【0.005).There were no differences between drugs in the rates of death, arterial thrombotic events and venous thrombotic events(P =0.41, P =0.55, P =0.10,respectively), while the rates of medical dictionary for regulatory activities(Med DAR) system organ class events and ≥1 systemic serious adverse events were higher in bevacizumab group than ranibizumab group(P 【0.05).But the incidences of death, arterial thrombotic events,venous thrombotic events, Med DAR system organ class events as well as ≥1 systemic serious adverse events were not statistically different between both treatment regimens of monthly and as needed(P =0.14, P =0.76,P =0.73, P =0.12, P =0.11, respectively).· CONCLUSION: Bevacizumab was equivalent to ranibizumab for BCVA, however bevacizumab tended to gain less decrease in CRT and had higher rates of serious adverse events. Compared with treatment as needed, treatment monthly showed superior efficacy in BCVA improvement and CRT reduction, while the rates of adverse events were similar in the two dosing regimens.

The complexities underlying age-related macular degeneration： could amyloid beta play an important role？

e-related macular degeneration （AMD） causes irreversible loss of central vision for which there is no effective treatment. Incipient pathology is thought to occur in the retina for many years before AMD manifests from midlife onwards to affect a large proportion of the elderly. Although genetic as well as non-genetic/environmental risks are recognized, its complex aetiology makes it difficult to identify susceptibility, or indeed what type of AMD develops or how quickly it progresses in different individuals. Here we summarize the literature describing how the Alzheimer＇s-linked amyloid beta （Aβ） group of misfolding proteins accumulate in the retina. The discovery of this key driver of Alzheimer＇s disease in the senescent retina was unexpected and surprising, enabling an altogether different perspective of AMD. We argue that Aβ fundamentally differs from other substances which accumulate in the ageing retina, and discuss our latest findings from a mouse model in which physiological amounts of Aβ were subretinally-injected to recapitulate salient features of early AMD within a short period. Our discoveries as well as those of others suggest the pattern of Aβ accumulation and pathology in donor aged/AMD tissues are closely reproduced in mice, including late-stage AMD phenotypes, which makes them highly attractive to study dynamic aspects of Aβ-mediated retinopathy. Furthermore, we discuss our findings revealing how Aβ behaves at single-cell resolution, and consider the long-term implications for neuroretinal function. We propose Aβ as a key element in switching to a diseased retinal phenotype, which is now being used as a biomarker for latestage AMD.

Risk Factors for Age-Related Macular Degeneration in Elderly Chinese Population in Shenyang of China

Objective The paper aims to evaluate the risk factors for age‐related macular degeneration （AMD） in elderly Chinese population in Shenyang,a northeast city of China.Methods A case‐control study was conducted to investigate the risk factors for the prevalence of AMD.Ninety three AMD patients diagnosed by a complete ophthalmic examination were recruited as cases from the outpatient departments of two eye hospitals in Shenyang,while 108 normal subjects of similar age and sex were recruited as controls.A questionnaire was administered among both cases and controls.Results AMD patients aged 60 years and older accounted for 75.3%.There were significantly higher educational levels,shorter smoking history,less sunlight exposure and cataract,and higher proportion of antioxidants intake in controls than in AMD patients.The frequency of intake of fruits,legumes,fish and shrimps was significantly higher in controls than in AMD patients.In a binary logistic regression analysis,smoking and cataract were the risk factors for AMD （OR：4.44,95% CI：2.27‐8.69;OR：4.47,95% CI：2.26‐8.85 respectively）.The high educational background was a protective factor for AMD （OR：0.761,95% CI：0.51‐0.98）.Conclusion A low educational background,smoking and cataract are associated with a higher prevalence of AMD.

Predictors of visual outcome in eyes with choroidal neovascularization secondary to age related macular degeneration treated with intravitreal bevacizumab monotherapy

AIM:To evaluate the predictors of visual improvement in eyes with naive choroidal neovascularization secondary to age-related macular degeneration (CNV -AMD) treated with intravitreal bevacizumab (IVB) monotherapy. METHODS:Fifty eyes with naive CNV-AMD with pretreatment best-corrected visual acuity (BCVA) better than 20/200 and treated with IVB monotherapy were evaluated. Several variables including age, sex, pre-treatment BCVA, CNV type and lesion size on fluorescein angiogram as well as SD-OCT parameters including pre-treatment central macular thickness (CMT), inner-segment/outer-segment (IS/OS) junction integrity, and external limiting membrane (ELM) integrity were analyzed to predict visual outcome.RESULTS:On univariate regression, pretreatment ELM damage was associated with less visual improvement after treatment (P =0.0145). However, ELM damage predicted only 10% of the visual outcome. On multivariate regression, pretreatment BCVA, IS/OS junction, and ELM integrity on SD-OCT were the significant predictors for the treatment effect and together predicted 37% of visual improvement. CONCLUSION:Pretreatment BCVA, ELM and IS/OS junction integrity on SD-OCT are of significant value inpredicting the visual improvement in naive wet AMD patients treated with IVB monotherapy.

Research progress of age-related macular degeneration related gene polymorphism at high altitude

Age-related macular degeneration(AMD)is a kind of progressive eye disease that seriously damages vision,and it is one of the important causes of blindness.In recent years,a large number of studies have found that there is a significant correlation between genetic factors and the occurrence and development of AMD.The study of gene polymorphism provides new ideas and directions for clinical diagnosis and treatment.In this paper,we will make a brief review of the research progress related to complement factor H(CFH),serine protease(HtrA1),age-related macular degeneration susceptibility factor 2(ARMS2)and vascular endothelial growth factor(VEGF)gene single nucleotide polymorphisms(SNP).

Evaluation of fundus autofluorescence patterns in age-related macular degeneration

AIM： To study the various morphological patterns of fundus autofluorescence （FAF） images in patients with age-related macular degeneration （AMD） in Indian population.METHODS： Totally 179 eyes of 104 patients with clinical diagnosis of AMD were recruited into the study. Autofluorescence images were captured using confocal scanning laser ophthalmoscope and the patterns of FAF were classified.RESULTS： Of 179 eyes, 27 （15.08%） were early AMD, 58 （32.41%） were intermediate AMD, 94 eyes （52.51%） were late AMD. Of 94 eyes with late AMD, 79 （84.04%） were neovascular AMD and 15 （15.96%） were central geographic atrophy. In eyes with early and intermediate AMD, 9 patterns of FAF were noted. Six patterns （normal, minimal change, focal increased, patchy increased, linear, reticular） were similar to that in the published classification. Two patterns （lacelike and speckled） described in the published classification were not found. Three new patterns （focal hypo-fluorescence, patchy hypo-fluorescence, mixed focal hypo-fluorescence and hyper-fluorescence） were detected. In eyes with neovascular AMD, 6 morphological patterns of FAF were noted. Two patterns （mixed hypo-fluorescence and hyper-fluorescence, central hypo-fluorescence with hyper-fluorescent rim） were similar to that in published classification. Two patterns （normal, near normal or normal background fluorescence in the centre of hypo-fluorescent area） described in the published classification were not found. Four new patterns （minimal change, hypo-fluorescent patch, central hypo-fluorescence with surrounding reticular, bull’s eye） were recognized. In eye with central geographic atrophy 5 morphological patterns were noted and these were similar to that in published classification.CONCLUSION： Phenotypic differences in the pattern of FAF exist in the study population compared to existing classification systems.

Matrix γ-carboxyglutamate protein and Fetuin-A, in wet type age-related macular degeneration

AIM: To evaluate the high sensitivity C-reactive protein(hs CRP), Fetuin-A and matrix γ-carboxyglutamate protein(MGP) as the main factors for vascular calcification and inflammation in serum of patients with advanced age-related macular degeneration(ARMD) in comparison to healthy controls. METHODS: The subjects were 40 patients with choroidal neovascularization(CNV) having a mean age of70.9 ±9.1y and a matched group of 49 apparently healthy control subjects. The ARMD was diagnosed using a slitlamp with superfield lens, fundus photography and fluorescein angiography. Measurement of hs CRP was done by nephelometry method. Levels of Fetuin-A and MGP were measured by enzyme-linked immunosorbent assay(ELISA) technique.RESULTS: hs CRP [0.45(0.07-2.63) mg/L vs 0.25(0.03-1.2) mg/L, P =0.02)] and Fetuin-A levels(50.27 ±5.04 vs44.99±10.28 ng/m L, P =0.009) were higher in the patients than in the control groups. We could not find significant difference in MGP level between two groups(P =0.08).There was not a significant correlation between MGP with Fetuin-A and hs CRP among the patients(P =0.7, P =0.9respectively). A significant negative correlation of hs CRP with Fetuin-A was observed in both case and control groups(P =0.004, r =-0.33 and P =0.001, r =-0.54,respectively).CONCLUSION: Although our study shows that serum hs CRP and Fetuin-A is increased in CNV patients as well as negatively correlated with both study groups, their direct role on pathogenesis of ARMD required future studies.

Vitreomacular Traction Post Intravitreal Bevacizumab for Age Related Macular Degeneration

Purpose: To report the significant worsening of Vitreomacular Traction (VMT), following the intravitreal injection of Bevacizumab (Avastin) in an Age Related Macular Degeneration (AMD) eye;thereby raising the awareness of this possibility. Method: Retrospective observational case report. Results: After 3 monthly doses of intravitreal injection of 1.25 mg/0.05 cc bevacizumab for treatment of AMD, a post injection OCT revealed the presence of VMT and an increased central macular thickness (CMT) by additional 268 microns compared to pre injection levels. Conclusion: Worsening of VMT and increase in CMT following injection of intravitreal drugs can occur. This VMT worsening effect of intravitreal injections is under recognized. It demands greater attention since it is seen with a new common route of ocular drug delivery and may be responsible for cases of pharmacological failure.

Amyloid beta deposition related retinal pigment epithelium cell impairment and subretinal microglia activation in aged APPswePS1 transgenic mice

AIM：To identify the pathological role of amyloid beta（Aβ） deposition in retinal degeneration,and explore Aβ deposition on the retinal pigment epithelium cells（RPE） layer and the associated structural and functional changes in Alzheimer＇s disease transgenic mice.METHODS：RPE changes in the eyes of APPswe/PS1 transgenic and none transgenic（NTG） mice over 20 months old were examined.Histological changes were investigated via hematoxylin and eosin（H＆E） staining and transmission electron microscopy（TEM） examination,whereas the expression of amyloid precursor protein（APP）,Aβ,Zonula occludens-1（ZO-1） and Ionized calcium binding adaptor molecule-1（IBA-1） were investigated using immunohistochemistry and immunofluorescence techniques.All of the obtained results were quantitatively and statistically analyzed.RESULTS：In aged transgenic mice,an APP-positive immunoreaction and Aβ deposition were detected on the RPE layer but were undetectable in NTG mice.The RPE demonstrated some vacuole changes,shortened basal infoldings and basal deposition in histopathological examination and TEM tests,wherein irregular shapes were indicated by ZO-1 disorganization through fluorescence.Furthermore,IBA-1 positive cells were observed to have accumulated and infiltrated into the RPE layer and localized beneath the RPE/Bruch＇s membrane（Br M） complex,which was accompanied by an increase in BrM thickness in aged transgenic mice in comparison to NTG mice.The IBA-1 positive cells were found to be co-stained with Aβ deposition on the RPE flat mounts.CONCLUSION：The observed Aβ deposition in the RPE layer may cause RPE dysfunction,which is associated with microglia cells infiltration into the retina of aged transgenic mice,suggesting that Aβ deposition probably plays a significant role in RPE-related degenerative disease.

Blue light induced retinal oxidative stress:Implications for macular degeneration

A number of studies have shown that oxidative stress can be harmful for the retina. The real causal circumstances that lead to degenerative diseases like age related macular degeneration remain obscure. Whether light induced radical stress is a direct interaction of light with photoreceptors or a secondary mechanism within the pigment epithelium or choroid is in discussion. Among the molecular mechanisms involved are production of reactive oxygen species(ROS), secondary lipid peroxidation, protein oxidation and DNA-damage. The initial trigger to write this review was first a recent finding of our group that the photoreceptor outer segments produce great amounts of ROS and second the detection of ectopic enzymes of the respiratory chainlocalized there- in addition to the hitherto known ROS sources like the visual pigments with their intermediates and the photoreceptor mitochondria harbouring the respiratory chain.

AB041.The implication of miRNA let-7f in retinal pigment epithelium degeneration under oxidative stress

Background:Age-related macular degeneration(AMD)is the most suspected cause of vision loss in the elderly.Given the considerable evidence,oxidative stress is thought to be a primary contributing factor to AMD.Retinal pigment epithelium(RPE)could be detrimentally compromised by oxidative stress along which blebs called retinal microparticles(RMPs)start to shed.In continue these particles would be taken by retina,causing RPE senescence,dysfunction and ultimately cell death.Along with the intracellular damages,accumulative deposit of microparticles in subretinal region can cause most known histological hallmark of dry AMD namely drusen.Based on our preliminary study,of 20 present miRNAs,Let-7f is the most abundant microRNAs in RMPs.As the accused substrate of RMPs through which retina function is compromised has yet to be well understood,we aimed to investigate pathophysiological role of let-7f and specific signaling triggered in RPE dysfunction.In brief,the principal objective is to further understand how RMPs implicate in RPE dysfunction.Methods:By oxidative stress inducing,RMPs were isolated from cultured ARPE-19 cells.We considered the effect of RMPs on ARPE-19 cells viability using MTT assay.In addition,to see whether RMPs effect could be ascribed to let-7f,ARPE-19 cells were transfected by carrier containing miRNA Let-7f.These transfected cells were then subjected senescence(β-galactosidase)and cell cycle assay to explore the molecular events responsible for Let-7f induced RPE cell dysfunction.Results:Regarding result we found that RMPs adversely affected RPE cell growth and resulted in significant decrease(≥30%)in cell viability.Let-7f-treated cells also revealed considerable increases of the senescence-associatedβ-galactosidase activity.Alongside RMPs impact,let-7f treatment group also showed similar result in cell growth.Conclusions:To the best of our knowledge,RPE cells uptake microparticles derived from oxidative-injured retinal cells,deteriorating integrity of vision compartments.Not only these finding would suggest that RMP’s impression likely corresponds to the miRNA let-7f,but introduce Let-7f as a mediator exacerbating the oxidative damages to RPE cells.This undesirable interplay is followed probably by dry AMD.Taken together,it seems by finding involved downstream pathways under RMPs pathogenesis,we can inhibit AMD disease in the early stage as well.In this line,we plan to investigate consecutive effect of RMP-associated miRNA inhibition in oxidative damage of retinal pigment epithelium.

Big DNA as a tool to dissect an age-related macular degeneration-associated haplotype

Age-related Macular Degeneration(AMD)is a leading cause of blindness in the developed world,especially in aging populations,and is therefore an important target for new therapeutic development.Recently,there have been several studies demonstrating strong associations between AMD and sites of heritable genetic variation at multiple loci,including a highly significant association at 10q26.The 10q26 risk region contains two genes,HTRA1 and ARMS2,both of which have been separately implicated as causative for the disease,as well as dozens of sites of non-coding variation.To date,no studies have successfully pinpointed which of these variant sites are functional in AMD,nor definitively identified which genes in the region are targets of such regulatory variation.In order to efficiently decipher which sites are functional in AMD phenotypes,we describe a general framework for combinatorial assembly of large‘synthetic haplotypes’along with delivery to relevant disease cell types for downstream functional analysis.We demonstrate the successful and highly efficient assembly of a first-draft 119kb wild-type‘assemblon’covering the HTRA1/ARMS2 risk region.We further propose the parallelized assembly of a library of combinatorial variant synthetic haplotypes covering the region,delivery and analysis of which will identify functional sites and their effects,leading to an improved understanding of AMD development.We anticipate that the methodology proposed here is highly generalizable towards the difficult problem of identifying truly functional variants from those discovered via GWAS or other genetic association studies.

Diverse roles of macrophages in intraocular neovasculardiseases:a review

Macrophages are involved in angiogenesis, and might also contribute to the pathogenesis of intraocular neovascular diseases. Recent studies indicated that macrophages exert different functions in the process of intraocular neovascularization, and the polarization of M1 and M2 phenotypes plays extremely essential roles in the diverse functions of macrophages. Moreover, a large number of cytokines released by macrophages not only participate in macrophage polarization, but also associate with retinal and choroidal neovascular diseases. Therefore, macrophage might be considered as a novel therapeutic target to the treatment of pathological neovascularization in the eye. This review mainly summarizes diverse roles of macrophages and discusses the possible mechanisms in retinal and choroidal neovascularization.

上皮-间质转化在视网膜下纤维化发病机制中的研究进展

视网膜下纤维化(SRFi)被定义为视网膜内或视网膜下混合的纤维血管结构,本质是新生血管性年龄相关性黄斑变性(nAMD)中脉络膜新生血管形成后伤口过度愈合的结果,这是导致nAMD患者终末期视力丧失的主要原因。nAMD患者终末期视网膜色素上皮细胞向上皮-间质细胞转化的过程被认为是影响SRFi形成的主要细胞基础。针对SRFi中上皮-间质转化的相关细胞及分子机制研究可能是未来终末期nAMD疾病防治的重要发展方向。