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Essential contribution of macrophage Tie2 signal mediated autophagy in laser-induced choroidal neovascularization
摘要： Autophagy plays critical roles in various ocular diseases, including age-related macular degeneration (AMD). Tie2-expressing macrophages (TEMs) play crucial roles in angiogenesis. To investigate the role of TEMs and autophagy in the development of AMD, we employed macrophage-specific Tie2 knockout mice and used a laser-induced choroidal neovascularization (CNV). The results showed that TEMs can promote CNV formation by up-regulating the level of autophagy. These results were further verified by in vitro cell experiments that peritoneal macrophages from Tie2 knockout mice can inhibit the expression of autophagy-related factors and inhibit the expression of angiogenic factor of VEGF by activating AMPK signaling pathway. Our results suggest that TEMs and macrophage Tie2 signal mediated-autophagy play critical role in experimental CNV, and they may be novel preventive targets for AMD treatment.
关键词： Tie2-expressing macrophage (TEMs),Age-related macular degeneration,Choroidal neovascularization,Autophagy
更新于2025-09-23 15:19:57
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A Circulating MicroRNA Profile in a Laser-Induced Mouse Model of Choroidal Neovascularization
摘要： Choroidal neovascularization (CNV) is a pathological process in which aberrant blood vessels invade the subretinal space of the mammalian eye. It is a characteristic feature of the prevalent neovascular age-related macular degeneration (nAMD). Circulating microRNAs (cmiRNAs) are regarded as potentially valuable biomarkers for various age-related diseases, including nAMD. Here, we investigated cmiRNA expression in an established laser-induced CNV mouse model. Upon CNV induction in C57Bl/6 mice, blood-derived cmiRNAs were initially determined globally by RNA next generation sequencing, and the most strongly dysregulated cmiRNAs were independently replicated by quantitative reverse transcription PCR (RT-qPCR) in blood, retinal, and retinal pigment epithelium (RPE)/choroidal tissue. Our findings suggest that two miRNAs, mmu-mir-486a-5p and mmur-mir-92a-3p, are consistently dysregulated during CNV formation. Furthermore, in functional in vitro assays, a significant impact of mmu-mir-486a-5p and mmu-mir-92a-3p on murine microglial cell viability was observed, while mmu-mir-92a-3p also showed an impact on microglial mobility. Taken together, we report a robust dysregulation of two miRNAs in blood and RPE/choroid after laser-induced initiation of CNV lesions in mice, highlighting their potential role in pathology and eventual therapy of CNV-associated complications.
关键词： cmiRNA regulation,biomarker,laser-induced choroidal,neovascularization,age-related macular degeneration
更新于2025-09-23 15:19:57
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Complement inhibition as a therapeutic strategy in retinal disorders
摘要： Introduction: Dry age-related macular degeneration (AMD) and Stargardt Macular Dystrophy (STGD1) result in vision loss, due to progressive atrophy of the macula and lack of effective treatments. Numerous studies have implicated complement-associated inflammation as a contributor to both diseases. Areas covered: The complement factor D inhibitor, lampalizumab, failed to halt geographic atrophy (GA) progression in phase 3 studies. The complement factor 3 (C3) inhibitor, APL-2, has shown potential to reduce GA growth in a phase 2 trial, supporting advancement to phase 3 trials. The intravenous complement factor 5 (C5) inhibitor, eculizumab, failed to halt GA progression in a phase 2 study. Another C5 inhibitor, avacincaptad pegol, is delivered by intravitreal injection, and will be studied for safety and preliminary signs of efficacy for AMD and STGD1 patients in phase 2 trials. LFG316 (C5 inhibitor) and CLG561 (properdin inhibitor) failed to halt GA progression in phase 2 studies. A phase 1 trial is evaluating the effects of combining LFG316 and CL561. Complement inhibition by gene therapy will be explored in the phase 1 trial of HMR59 in AMD patients. Expert opinion: While complement inhibition has not yet demonstrated ability to halt GA progression in a phase 3 trial, further study is warranted.
关键词： Age-related macular degeneration,Stargardt Macular Dystrophy,geographic atrophy,LFG316,CL561,avacincaptad pegol,eculizumab,complement,APL-2,lampalizumab
更新于2025-09-19 17:15:36
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Treatment of neovascular age-related macular degeneration with anti-VEGF agents: retrospective analysis of 5-year outcomes
摘要： Purpose: To evaluate the 5-year results obtained in clinical practice in the treatment of neovascular age-related macular degeneration (nAMD) with anti-VEGF agents. Materials and methods: We retrospectively analyzed all patients with nAMD who initiated anti-VEGF treatment before October 2009. We collected data regarding visual and anatomical outcomes. Results: A total of 278 patients met the selection criteria. The mean number of intravitreal injections was 5.7 in the first year and 3.7 in the fifth year. A positive mean visual acuity variation of +3.7 Early Treatment Diabetic Retinopathy Study letters occurred in the first year, but no significant differences relative to baseline were observed thereafter. The majority of patients (71%) maintained stable visual acuity throughout follow-up. At 5 years, mean central macular thickness remained substantially inferior to baseline (-96.6 μm), and 56% of patients maintained dry retinas. Conclusion: Anti-VEGF therapy leads to long-term visual stabilization in the great majority of patients.
关键词： visual acuity,vascular endothelial growth factor,choroidal neovascularization,age-related macular degeneration
更新于2025-09-19 17:15:36
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Physician, patient, and caregiver experience of different wet age-related macular degeneration anti-VEGF treatment regimens in Japan: a qualitative assessment
摘要： Purpose: The purpose of this study was to monitor anti-vascular endothelial growth factor (anti-VEGF) treatment regimens for wet age-related macular degeneration (wAMD) in clinical practice and to determine how they impact the physician, patient, and caregiver treatment experience. Materials and methods: This was a qualitative analysis based on semistructured interviews with 20 ophthalmologists who had practiced both pro re nata (PRN) and treat-and-extend (T&E) anti-VEGF regimens for wAMD. Interview questions were constructed to assess how the different regimens affected patient and caregiver experiences (in the opinion of the ophthalmologist) in addition to the ophthalmologist’s own experience. The interview included questions relating to 1) issues and benefits of PRN and T&E; 2) logistical and operational issues of introducing proactive therapy, especially T&E, to PRN practice; and 3) actions taken to handle the issues raised in 2). Results: A total of 18 interview results were eligible for analysis. The study demonstrated that the benefits of T&E compared with PRN included decreased burden of patient consultations, decreased patient and caregiver emotional burden, and a sustained period of macular dryness. The issues associated with T&E were increased number of injections and financial burden from prolonged treatment duration. The ophthalmologists also experienced difficulty explaining the significance of proactive injections to patients. Countermeasures to operational issues experienced by ophthalmologists varied by practice. Conclusion: Patients, caregivers, and the practicing ophthalmologists experienced benefits associated with a T&E regimen. However, in order to encourage better understanding of the T&E regimen, including its smooth implementation and significance for patients, a formal T&E treatment guideline providing standard practice should be considered.
关键词： wAMD patient experience,wet age-related macular degeneration,anti-VEGF as-needed,anti-vascular growth factor,anti-VEGF treat-and-extend
更新于2025-09-19 17:15:36
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Mechanisms Underlying the Visual Benefit of Cell Transplantation for the Treatment of Retinal Degenerations
摘要： The transplantation of retinal cells has been studied in animals to establish proof of its potential benefit for the treatment of blinding diseases. Photoreceptor precursors have been grafted in animal models of Mendelian-inherited retinal degenerations, and retinal pigmented epithelial cells have been used to restore visual function in animal models of age-related macular degeneration (AMD) and recently in patients. Cell therapy over corrective gene therapy in inherited retinal degeneration can overcome the genetic heterogeneity by providing one treatment for all genetic forms of the diseases. In AMD, the existence of multiple risk alleles precludes a priori the use of corrective gene therapy. Mechanistically, the experiments of photoreceptor precursor transplantation reveal the importance of cytoplasmic material exchange between the grafted cells and the host cells for functional rescue, an unsuspected mechanism and novel concept. For transplantation of retinal pigmented epithelial cells, the mechanisms behind the therapeutic benefit are only partially understood, and clinical trials are ongoing. The fascinating studies that describe the development of methodologies to produce cells to be grafted and demonstrate the functional benefit for vision are reviewed.
关键词： retinitis pigmentosa,photoreceptors,retinal pigmented epithelium,age-related macular degeneration,cytoplasmic material transfer,induced-pluripotent stem cells
更新于2025-09-19 17:15:36
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Henle Fiber Layer Phase Retardation Changes Associated With Age-Related Macular Degeneration
摘要： PURPOSE. To quantify and compare phase retardation amplitude and regularity associated with the Henle fiber layer (HFL) between nonexudative AMD patients and age-matched controls using scanning laser polarimetry (SLP) imaging. METHODS. A scanning laser polarimeter was used to collect 15 × 15° macular-centered images in 25 patients with nonexudative AMD and 25 age-matched controls. Raw image data were used to compute macular phase retardation maps associated with the HFL. Consecutive, annular regions of interest from 0.5 to 3.0° eccentricity, centered on the fovea, were used to generate intensity profiles from phase retardation data and analyzed with two complementary techniques: a normalized second harmonic frequency (2f) of the fast Fourier Transform (FFT) analysis and a curve fitting analysis using a 2f sine function. Paired t-tests were used to compare the normalized 2f FFT magnitude at each eccentricity between the two groups, the eccentricity that yielded the maximum normalized 2f FFT between paired individuals across the two groups, and curve fitting RMS error at each eccentricity between the two groups. RESULTS. Normalized 2f FFT components were lower in the AMD group at each eccentricity, with no difference between the two groups in the maximum normalized 2f FFT component eccentricity. The root-mean-square (RMS) error from curve fitting was significantly higher in the AMD group. CONCLUSIONS. Phase retardation changes in the central macula indicate loss and/or structural alterations to central cone photoreceptors in nonexudative AMD patients. Scanning laser polarimetry imaging is a noninvasive method for quantifying cone photoreceptor changes associated with central macular disease.
关键词： scanning laser polarimetry,age-related macular degeneration,Henle fiber layer,photoreceptors
更新于2025-09-19 17:15:36
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Autofluorescence Lifetimes in Geographic Atrophy in Patients With Age-Related Macular Degeneration
摘要： PURPOSE. To investigate fluorescence lifetime characteristics in patients with geographic atrophy (GA) in eyes with age-related macular degeneration and to correlate the measurements with clinical data and optical coherence tomography (OCT) findings. METHODS. Patients with GA were imaged with a fluorescence lifetime imaging ophthalmoscope. Retinal autofluorescence lifetimes were measured in a short and a long spectral channel (498–560 nm and 560–720 nm). Mean retinal fluorescence lifetimes were analyzed within GA and the surrounding retina, and data were correlated with best corrected visual acuity and OCT measurements. RESULTS. Fluorescence lifetime maps of 41 eyes of 41 patients (80 ± 7 years) with GA were analyzed. Mean lifetimes within areas of atrophy were prolonged by 624 ± 276 ps (+152%) in the short spectral channel and 418 ± 186 ps (+83%) in the long spectral channel compared to the surrounding tissue. Autofluorescence lifetime abnormalities in GA occurred with particular patterns, similar to those seen in fundus autofluorescence intensity images. Within the fovea short mean autofluorescence lifetimes were observed, presumably representing macular pigment. Short lifetimes were preserved even in the absence of foveal sparing but were decreased in patients with advanced retinal atrophy in OCT. Short lifetimes in the fovea correlated with better best corrected visual acuity in both spectral channels. CONCLUSIONS. This study established that autofluorescence lifetime changes in GA present with explicit patterns. We hypothesize that the short lifetimes seen within the atrophy may be used to estimate damage induced by atrophy and to monitor disease progression in the context of natural history or interventional therapeutic studies.
关键词： GA,geographic atrophy,ophthalmic imaging,fundus autofluorescence,fluorescence lifetimes,AMD,age-related macular degeneration
更新于2025-09-19 17:15:36
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Impacts of impaired face perception on social interactions and quality of life in age-related macular degeneration: A qualitative study and new community resources
摘要： Aims Previous studies and community information about everyday difficulties in age-related macular degeneration (AMD) have focussed on domains such as reading and driving. Here, we provide the first in-depth examination of how impaired face perception impacts social interactions and quality of life in AMD. We also develop a Faces and Social Life in AMD brochure and information sheet, plus accompanying conversation starter, aimed at AMD patients and those who interact with them (family, friends, nursing home staff). Method Semi-structured face-to-face interviews were conducted with 21 AMD patients covering the full range from mild vision loss to legally blind. Thematic analysis was used to explore the range of patient experiences. Results Patients reported faces appeared blurred and/or distorted. They described recurrent failures to recognise others’ identity, facial expressions and emotional states, plus failures of alternative non-face strategies (e.g., hairstyle, voice). They reported failures to follow social nuances (e.g., to pick up that someone was joking), and feelings of missing out (’I can’t join in’). Concern about offending others (e.g., by unintentionally ignoring them) was common, as were concerns of appearing fraudulent (’Other people don’t understand’). Many reported social disengagement. Many reported specifically face-perception-related reductions in social life, confidence, and quality of life. All effects were observed even with only mild vision loss. Patients endorsed the value of our Faces and Social Life in AMD Information Sheet, developed from the interview results, and supported future technological assistance (digital image enhancement). Conclusion Poor face perception in AMD is an important domain contributing to impaired social interactions and quality of life. This domain should be directly assessed in quantitative quality of life measures, and in resources designed to improve community understanding. The identity-related social difficulties mirror those in prosopagnosia, of cortical rather than retinal origin, implying findings may generalise to all low-vision disorders.
关键词： qualitative study,quality of life,face perception,social interactions,community resources,age-related macular degeneration
更新于2025-09-19 17:15:36
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Prognostic phenotypic and genotypic factors associated with photodynamic therapy response in patients with age-related macular degeneration
摘要： Background: This study aimed to demonstrate the phenotypic and genotypic factors associated with photodynamic therapy (PDT) for age-related macular degeneration (AMD). Methods: The study included 149 patients with exudative AMD treated by PDT. Eight phenotypic factors and ten genotypic factors for three single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996) in the complement factor H (CFH) gene, rs 11200638-SNP in the high temperature requirement A-1 (HTRA1) gene, two SNPs (rs699947, rs2010963) in the vascular endothelial growth factor (VEGF) gene, and four SNPs (rs12948385, rs12150053, rs9913583, rs1136287) in the pigment epithelium-derived factor (PEDF) gene were evaluated. Results: A significant association with best-corrected visual acuity change was demonstrated in the greatest linear dimension, presence or absence of pigment epithelial detachment, and HTRA1-rs11200638 genotype statistically (P=3.67×10-4, 1.95×10-2, 1.24×10-3, respectively). Best-corrected visual acuity in patients with AA genotype of HTRA1-rs11200638 significantly decreased compared with that in patients with GG genotype (P=1.33×10-3). Logistic regression analyses demonstrated HTRA1-rs11200638 genotype was most strongly associated with best-corrected visual acuity outcome from baseline at 12 months after photodynamic therapy (P=4.60×10-3; odds ratio 2.363; 95% confidence interval 1.303–4.285). Conclusion: The HTRA1-rs11200638 variant showed the most significant association. Therefore, this variant may be used as a prognostic factor to estimate the PDT response with significant predictive power.
关键词： pigment epithelial detachment,photodynamic therapy,phenotypic and genotypic factors,greatest linear dimension,high temperature requirement A-1,age-related macular degeneration
更新于2025-09-19 17:15:36