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1.
FASEB J ; 38(1): e23389, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38153347

RESUMO

Serum amyloid A (SAA) are major acute-phase response proteins which actively participate in many inflammatory diseases. This study was designed to explore the function of SAA in acute ocular inflammation and the underlying mechanism. We found that SAA3 was upregulated in endotoxin-induced uveitis (EIU) mouse model, and it was primarily expressed in microglia. Recombinant SAA protein augmented intraocular inflammation in EIU, while the inhibition of Saa3 by siRNA effectively alleviated the inflammatory responses and rescued the retina from EIU-induced structural and functional damage. Further study showed that the recombinant SAA protein activated microglia, causing characteristic morphological changes and driving them further to pro-inflammatory status. The downregulation of Saa3 halted the amoeboid change of microglia, reduced the secretion of pro-inflammatory factors, and increased the expression of tissue-reparative genes. SAA3 also regulated the autophagic activity of microglial cells. Finally, we showed that the above effect of SAA on microglial cells was at least partially mediated through the expression and signaling of Toll-like receptor 4 (TLR4). Collectively, our study suggested that microglial cell-expressed SAA could be a potential target in treating acute ocular inflammation.


Assuntos
Microglia , Proteína Amiloide A Sérica , Animais , Camundongos , Proteína Amiloide A Sérica/genética , Inflamação/induzido quimicamente , Retina , Proteínas de Fase Aguda , Endotoxinas/toxicidade
2.
Exp Eye Res ; 245: 109985, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945518

RESUMO

Aging is a major risk factor for the development or the worsening of retinal degenerative conditions. The intricate network of the neural retina determined that the retinal aging is a complicated process. The aim of this study is to delineate the transcriptomic changes of major retinal neurons during aging in C57BL/6 mice at single-cell level. We analyzed the transcriptional profiles of the photoreceptor, bipolar, amacrine, and Müller glial cells of 1.5-2 and 24-30 months old mice using single-cell RNA sequencing technique. We selectively confirmed the differences in gene expression using immunofluorescence staining and RNA in situ hybridization analysis. We found that each retinal cell type had unique changes upon aging. However, they all showed signs of dysregulated glucose and energy metabolism, and perturbed proteostasis. In particular, old Müller glia exhibited the most profound changes, including the upregulation of cell metabolism, stress-responses, antigen-presentation and immune responses and metal ion homeostasis. The dysregulated gliogenesis and differentiation was confirmed by the presence of Müller glia expressing rod-specific genes in the inner nuclear layer and the outer plexiform layer of the old retina. We further pinpointed the specific loss of GABAergic amacrine cells in old retina. Our study emphasized changes of amacrine and Müller glia during retinal aging, provided resources for further research on the molecular and cellular regulatory mechanisms underlying aging-associated retinal deterioration.

3.
J Med Genet ; 60(2): 174-182, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35361685

RESUMO

BACKGROUND: Familial exudative vitreoretinopathy (FEVR) is an inheritable blinding disorder with clinical and genetic heterogeneity. Heterozygous variants in the CTNNB1 gene have been reported to cause FEVR. However, the pathogenic basis of CTNNB1-associated FEVR has not been fully explored. METHODS: Whole-exome sequencing was performed on the genomic DNA of probands. Dual-luciferase reporter assay, western blotting and co-immunoprecipitation were used to characterise the impacts of variants. Quantitative real-time PCR, EdU (5-ethynyl-2'-deoxyuridine) incorporation assay and immunocytochemistry were performed on the primary human retinal microvascular endothelial cells (HRECs) to investigate the effect of CTNNB1 depletion on the downstream genes involved in Norrin/ß-catenin signalling, cell proliferation and junctional integrity, respectively. Transendothelial electrical resistance assay was applied to measure endothelial permeability. Heterozygous endothelial-specific Ctnnb1-knockout mouse mice were generated to verify FEVR-like phenotypes in the retina. RESULTS: We identified two novel heterozygous variants (p.Leu103Ter and p.Val199LeufsTer11) and one previously reported heterozygous variant (p.His369ThrfsTer2) in the CTNNB1 gene. These variants caused truncation and degradation of ß-catenin that reduced Norrin/ß-catenin signalling activity. Additionally, knockdown (KD) of CTNNB1 in HRECs led to diminished mRNA levels of Norrin/ß-catenin targeted genes, reduced cell proliferation and compromised junctional integrity. The Cre-mediated heterozygous deletion of Ctnnb1 in mouse endothelial cells (ECs) resulted in FEVR-like phenotypes. Moreover, LiCl treatment partially rescued the defects in CTNNB1-KD HRECs and EC-specific Ctnnb1 heterozygous knockout mice. CONCLUSION: Our findings reinforced the current pathogenesis of Norrin/ß-catenin for FEVR and expanded the causative variant spectrum of CTNNB1 for the prenatal diagnosis and genetic counselling of FEVR.


Assuntos
Doenças Retinianas , beta Catenina , Humanos , Animais , Camundongos , Vitreorretinopatias Exsudativas Familiares/genética , beta Catenina/genética , Células Endoteliais , Retina , Fenótipo , Mutação , Linhagem , Análise Mutacional de DNA , Doenças Retinianas/genética
4.
Clin Genet ; 103(3): 320-329, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36453149

RESUMO

Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder; however, the known FEVR-associated variants account for approximately only 50% cases. Currently, the pathogenesis of most reported variants is not well studied, we aim to identify novel variants from FEVR-associated genes and perform a comprehensive functional analysis to uncover the pathogenesis of variants that cause FEVR. Using targeted gene panel and Sanger sequencing, we identified six novel and three known variants in TSPAN12 and NDP. These variants were demonstrated to cause significant inhibition of Norrin/ß-catenin pathway by dual-luciferase reporter assay and western blot analysis. Structural analysis and co-immunoprecipitation revealed compromised interactions between missense variants and binding partners in the Norrin/ß-catenin pathway. Immunofluorescence and subcellular protein extraction were performed to reveal the abnormal subcellular trafficking. Additionally, over-expression of TSPAN12 successfully enhanced the Norrin/ß-catenin signaling activity by strengthening the binding affinity of mutant Norrin with FZD4 or LRP5. Together, these observations expanded the spectrum of FEVR-associated variants for the genetic counseling and prenatal diagnosis of FEVR, as well providing a potential therapeutic strategy for the treatment of FEVR.


Assuntos
Oftalmopatias Hereditárias , Doenças Retinianas , Humanos , beta Catenina/genética , Análise Mutacional de DNA , Oftalmopatias Hereditárias/genética , Proteínas do Olho/genética , Vitreorretinopatias Exsudativas Familiares/genética , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Mutação , Proteínas do Tecido Nervoso/genética , Linhagem , Doenças Retinianas/genética , Tetraspaninas/genética , Tetraspaninas/metabolismo
5.
FASEB J ; 36(5): e22257, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35471770

RESUMO

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness associated with retinal vaso-obliteration in phase 1 and pathological neovascularization (NV) in phase 2; however, effective and safe treatments for ROP definitive treatment are yet to be determined. Anti-vascular endothelial growth factor (VEGF) therapy mainly focuses on reducing abnormal NV in phase 2 but with high risks of late recurrence and systemic side effects. Previous studies have established that the severity of vaso-obliteration in phase 1 largely influences subsequent stages, suggesting that prevention of vessels loss may be a potential therapeutic target for ROP. Herein, the therapeutic potential and safety of early Elabela intervention treatment in treating phase 1 ROP and the possible underlying mechanisms were investigated using an oxygen-induced retinopathy (OIR) mouse model. It was observed that intraperitoneal injection of Elabela remarkably reduced the avascular retinal area and increased the vascular density in phase 1 of OIR mice. Further investigation revealed that mitochondrion-dependent ferroptosis was involved in oxidative stress-mediated vascular protection loss in phase 1 OIR. Furthermore, we demonstrated that Elabela could rescue mitochondria-dependent ferroptosis via mediating the xCT/GPX4 axis. Collectively, our study revealed that ferroptosis may play a significant role in early ROP, while Elabela may be a safe and promising strategy for the early intervention of ROP.


Assuntos
Ferroptose , Neovascularização Retiniana , Retinopatia da Prematuridade , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Humanos , Recém-Nascido , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/metabolismo , Oxigênio/metabolismo , Neovascularização Retiniana/metabolismo , Vasos Retinianos/metabolismo , Retinopatia da Prematuridade/tratamento farmacológico
6.
Retina ; 43(1): 138-143, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31929414

RESUMO

PURPOSE: To report a novel use of an iris speculum to assist with membrane dissection and trough separation for stage 5 retinopathy of prematurity-related funnel-shaped tractional retinal detachment complicated with pupillary adhesion. METHODS: Limbus-based closed vitrectomy and membrane dissection were performed in 10 eyes (9 patients) with stage 5 retinopathy of prematurity-related tractional retinal detachment and pupillary adhesion. After synechiolysis, an iris speculum was positioned to enlarge the pupil for surgical visualization and maintain a neutral iris plane. The retrolental membrane was dissected bimanually and circumferentially along the peripheral trough and then toward the central retina with vertical scissors and end-gripping forceps. RESULTS: In all 10 eyes, retrolental membranes were entirely removed and troughs were circumferentially unraveled. Follow-up examinations performed 6 to 18 months postoperatively showed reattachment of the retina in 3 eyes with an open-narrow funnel and 6 of 7 eyes with a narrow-narrow funnel. A near-circular pupil without recurrent pupillary adhesion was preserved in all nine eyes showing retinal reattachment. CONCLUSION: This use of the iris speculum effectively exposes the surgical field for the entire removal of retrolental tissue and interruption of the peripheral trough in stage 5 retinopathy of prematurity-related tractional retinal detachment complicated with pupillary adhesion. The pupil's configuration is well preserved postoperatively.


Assuntos
Descolamento Retiniano , Retinopatia da Prematuridade , Recém-Nascido , Humanos , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Descolamento Retiniano/cirurgia , Retinopatia da Prematuridade/complicações , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/cirurgia , Pupila , Iris/cirurgia , Vitrectomia/efeitos adversos , Instrumentos Cirúrgicos/efeitos adversos
7.
Retina ; 43(3): 523-528, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32516225

RESUMO

PURPOSE: To report viscodelamination of localized retrolental plaques during lens-sparing vitrectomy in eyes with pediatric tractional vitreoretinopathy. METHODS: Viscodelamination of retrolental plaques was performed during 23-gauge lens-sparing vitrectomy in 11 eyes from 11 children with a median age (range) of 12 (4-58) months. There were five eyes with Stage 4 familial exudative vitreoretinopathy, one eye with Stage 4B retinopathy of prematurity, and five eyes with anterior-posterior persistent fetal vasculature syndrome. Retrolental plaques were separated from the posterior lens capsule by the tension of viscoelastic injection in the Berger's space. RESULTS: In 10 of 11 eyes, retrolental plaques were removed from posterior surface of lens without capsular tearing. During the 12-month to 18-month follow-up period, lens clarity along the visual axis was retained in 5 eyes with familial exudative vitreoretinopathy, one eye with retinopathy of prematurity, and 2 of 5 eyes with persistent fetal vasculature. Atraumatic viscodelamination was associated with retrolental plaques that did not incorporate into the posterior lens capsule. Retinal dragging was reversed in all 11 eyes. CONCLUSION: Viscodelamination may be effective for the dissection of retrolental plaques related to pediatric vitreoretinopathy in selected cases.


Assuntos
Doenças do Tecido Conjuntivo , Doenças Orbitárias , Vítreo Primário Hiperplásico Persistente , Descolamento Retiniano , Retinopatia da Prematuridade , Recém-Nascido , Humanos , Criança , Lactente , Vitrectomia , Vitreorretinopatias Exsudativas Familiares/complicações , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/cirurgia , Retinopatia da Prematuridade/complicações , Acuidade Visual , Estudos Retrospectivos , Vítreo Primário Hiperplásico Persistente/diagnóstico , Vítreo Primário Hiperplásico Persistente/cirurgia , Doenças do Tecido Conjuntivo/complicações , Descolamento Retiniano/cirurgia , Seguimentos , Resultado do Tratamento
8.
Retina ; 43(4): 698-704, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35174806

RESUMO

BACKGROUND/PURPOSE: To report an intraoperative perfluorocarbon liquid (PFCL) tamponade technique in treating extensive retinal detachment secondary to a myopic macular hole (MH) through pars plana vitrectomy. METHODS: The technique was applied in nine eyes with MH-RD extending two quadrants or more areas. The procedures for pars plana vitrectomy included: 1). thorough drainage of subretinal fluid through the MH with fluid-air exchange; 2). PFCL tamponade on the macular area for more than 10 minutes; and 3). repairing the MH after PFCL was removed. RESULTS: All nine eyes gained intraoperative retinal reattachment after PFCL tamponade for 22.22 ± 8.01 minutes and removal of PFCL. Procedures for MH closure included internal limiting membrane peeling in eight eyes, with internal limiting membrane free flap insertion (four eyes), internal limiting membrane inverted flap insertion (two eyes), or lens capsular flap transplantation (three eyes). All eyes received C3F8 tamponade. During 9.11 ± 3.89 months of follow-up, eight of the nine eyes (89%) achieved retinal reattachment and MH closure; one eye achieved anatomical success after reoperations. All eyes had vision improvement at the last follow-up. CONCLUSION: This new technique in pars plana vitrectomy may promote anatomical and functional recovery in the treatment of extensive retinal detachment secondary to a myopic MH.


Assuntos
Fluorocarbonos , Miopia Degenerativa , Descolamento Retiniano , Perfurações Retinianas , Humanos , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Descolamento Retiniano/cirurgia , Perfurações Retinianas/complicações , Perfurações Retinianas/diagnóstico , Acuidade Visual , Vitrectomia/métodos , Estudos Retrospectivos
9.
Retina ; 43(11): 2010-2018, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37870909

RESUMO

PURPOSE: To explore the etiologies, characteristics, and prognosis of lamellar macular hole (LMH) in pediatric patients. METHODS: A consecutive series of 59 patients (62 eyes) aged <16 years with MHs (lamellar and full-thickness) treated from 2013 to 2021 in a tertiary center was reviewed. Data collected included demographic and clinical characteristics, management, and outcomes of patients presenting with LMH. RESULTS: Twelve eyes (19.4%) of 11 children had LMH. Seven patients were male, with an average age of 6.9 years. The primary pathologies included X-linked retinoschisis in six eyes (50%); familial exudative vitreoretinopathy in two (16.7%); and ocular toxocariasis, Coats disease, persistent hyperplastic primary vitreous, and idiopathic LMH with associated lenticonus in one eye (8.3%) each. Four eyes (36.4%) showed tractional appearance and seven (63.6%) degenerative. All degenerative LMH showed ellipsoidal zone defect, significantly higher than that in the tractional group (25%, 1/4) ( P = 0.024). Five eyes achieved closed LMH and limited visual gain, four underwent surgery, and one closed spontaneously. CONCLUSION: X-linked retinoschisis was the most frequent primary cause in pediatric LMH. Two types of LMH can be classified: tractional and degenerative. The latter showed a higher rate of ellipsoidal zone defect. Vision improved after LMH closed, regardless of surgery or spontaneous closure.


Assuntos
Membrana Epirretiniana , Macula Lutea , Perfurações Retinianas , Retinosquise , Humanos , Masculino , Criança , Feminino , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/etiologia , Perfurações Retinianas/cirurgia , Estudos Retrospectivos , Acuidade Visual , Retinosquise/etiologia , Retinosquise/complicações , Tomografia de Coerência Óptica , Macula Lutea/patologia , Membrana Epirretiniana/cirurgia , Seguimentos , Vitrectomia/efeitos adversos
10.
Retina ; 43(2): 191-199, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36695790

RESUMO

PURPOSE: To compare the functional and anatomical outcomes of peeled internal limiting membrane reposition and traditional internal limiting membrane peeling for the treatment of idiopathic macular hole. METHODS: This is a randomized, single-center, and double-blinded, pilot, controlled trial. RESULTS: Of the 30 patients enrolled, 27 (13 in Group 1 and 14 in Group 2) were included in the primary analysis (22 women [81.5%]; mean [SD] age, 61.7 [6.8] years). The BCVA was 0.23 ± 0.18 logMAR in the reposition group and 0.44 ± 0.24 logMAR in the peeling group at 6 months postoperatively (P = 0.02). The primary MH closure rate is 86.7% in the reposition group and 93.3% in the peeling group (P = 0.60). The range of the inner retinal dimpling was significantly lower in the reposition group at 6 months postoperatively (P < 0.0001). The thickness of the full parafovea (P = 0.0092), inner parafovea (P = 0.0007), inner perifovea (P = 0.0044), and outer fovea (P = 0.0392) was significantly greater in the reposition group than that in the peeling group at 6 months postoperatively. The sensitivity threshold and mfERG P1 wave amplitude density in rings one, four, and five were higher in the reposition group than in the peeling group at 6 months postoperatively. CONCLUSION: Our findings suggest that the novel technique of peeled internal limiting membrane reposition has advantages over the traditional internal limiting membrane peeling in better microstructural outcomes of inner retina and functional recoveries. Furthermore, larger RCT studies are warranted.


Assuntos
Perfurações Retinianas , Humanos , Feminino , Pessoa de Meia-Idade , Perfurações Retinianas/cirurgia , Projetos Piloto , Resultado do Tratamento , Vitrectomia/métodos , Acuidade Visual , Retina , Tomografia de Coerência Óptica/métodos , Membrana Basal/cirurgia , Estudos Retrospectivos
11.
Retina ; 43(12): 2075-2079, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-35174805

RESUMO

PURPOSE: We present a new technique that allows an intraocular lens to be explanted through the small incisions used in modern cataract surgery. METHODS AND RESULTS: The intraocular lens optic is cut into three connected pieces at the 1-mm-wide end with scissors. Then, with the stabilizing counterforce provided by a pair of vitreoretinal forceps through a paracentesis, the middle piece is removed first, followed by the two side pieces connected with haptics flipped over at the connected part. These two parts overlap each other when passing through the incision, eventually resulting in the explantation of the intraocular lens, as an intact piece. CONCLUSION: We believe this method provides a simple and effective way to remove intraocular lens through very small incisions, which could also reduce complications and hasten patient's recovery.


Assuntos
Extração de Catarata , Lentes Intraoculares , Humanos , Reoperação , Remoção de Dispositivo/métodos , Olho
12.
J Craniofac Surg ; 34(8): 2379-2383, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37639658

RESUMO

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Our study attempted to analyze the research trends in HNSCC and compare contributions from different countries, institutions, journals, and authors. MATERIALS AND METHODS: The authors extracted publications in this field from 2002 to 2022 from the Web of Science database. Microsoft Excel and VOSviewer were performed to collect data on publication numbers, analyze publication trends, and visualize relevant results. RESULTS: A total of 1903 publications were screened. In the past 20 years, the United States contributed the most publications and citations in the HNSCC research. China ranked second in the number of publications. The Ophthalmic Plastic and Reconstructive Surgery was the most productive journal concerning HNSCC. ESMAELIB of the University of Texas System and ROSENTHAL EL of Stanford University had published the most publications in this field. Keywords were categorized into 3 clusters: basic study, clinical feature study, and treatment-related study. The keywords "reflectance confocal microscopy", "raman-spectroscopy", and "confocal laser endomicroscopy" were most frequently emerged in the recent years. Management-related research has been recognized as a potential focus in the HNSCC.


Assuntos
Bibliometria , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , China , Bases de Dados Factuais , Neoplasias de Cabeça e Pescoço/cirurgia
13.
Int Ophthalmol ; 43(9): 3263-3268, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37178407

RESUMO

PURPOSE: To describe the characteristics and clinical course of retinopathy of prematurity (ROP)-like ridges in healthy full-term newborns. METHODS: A retrospective medical record review was performed on newborns who underwent fundus photography within 72 h of birth between January 1st and December 31st, 2019 at Women & Children's Health Care Hospital of Huantai, China. The RetCam 3 wide-field digital imaging system was used for fundus photography. ROP-like ridges were discovered and described. RESULTS: Total of 5507 full-term infants underwent fundus photography. ROP-like ridges were discovered in 90 eyes from 57 infants (1.0%). Stage 1 ROP-like was seen in 63 of the eyes (70%), Stage 2 ROP-like in 26 of the eyes (28.9%), and Stage 3 ROP-like in 1 eye (1.1%). These ROP-like ridges were found in Zone II (41.1%) and Zone III (58.9%), but not in Zone I. Eight (8.9%) of the eyes had pre-plus-like diseases. No eyes had plus disease. All ROP-like ridges and pre-plus-like diseases were spontaneously regressed with a mean duration of 39.0 ± 8.2 days. Male sex (P = 0.003) was positively associated with ROP-like changes. CONCLUSION: Healthy full-term newborns may have incomplete retinal vascularization and ROP-like ridges at birth. These ROP-like ridges showed signs of spontaneous regression.


Assuntos
Neovascularização Retiniana , Retinopatia da Prematuridade , Lactente , Criança , Recém-Nascido , Humanos , Masculino , Feminino , Retinopatia da Prematuridade/diagnóstico , Recém-Nascido Prematuro , Estudos Retrospectivos , Neovascularização Retiniana/diagnóstico , Olho , Idade Gestacional
14.
Exp Cell Res ; 408(1): 112783, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469714

RESUMO

Retinopathy of prematurity (ROP) is a severe retinal dysfunction in prematurely born babies. The relationship between non-coding RNAs and retinopathy of prematurity (ROP) remain unclear. Microarray analysis of lncRNAs, miRNAs, and mRNAs was conducted in a mouse model of ROP. A competing endogenous RNA (ceRNA) network was constructed. The relationship among MALAT1, miR-124-3p, and Early growth response protein 1 (EGR1) was assessed in hypoxia-induced primary human umbilical vein endothelial cells (HUVECs) and ROP mouse model. In the study, we found 2252 lncRNAs, 1239 mRNAs, and 36 miRNAs were differentially regulated. ceRNA network consisting of 21 lncRNAs, 10 miRNAs, and 19 mRNAs was established. Of the most down-regulated miRNAs, miR-124-3p was selected for additional study. miR-124-3p ceased the migration and proliferation of primary HUVECs in hypoxic conditions, and directly suppressed EGR1. Additionally, MALAT1 directly sponged miR-124-3p. Knockdown of MALAT1 decreased EGR1 expression and inhibited the migration and proliferation of primary HUVECs in hypoxia. Furthermore, these changes were rescued by depletion of miR-124-3p. In vivo, intravitreal injection of miR-124-3p, shMALAT1 decreased EGR1 expression and markedly suppressed retinal neovascularization in OIR models. Intravitreal injection of shMALAT1 and miR-124-3p antagomir at the same time can promote retinal neovascularization, which reversed the suppression of retinal neovascularization functioned by shMALAT1. In conclusion, the expression profiles of lncRNAs and miRNAs and the ceRNA network in a mouse model of ROP may be indicative of the underlying mechanisms of retinal angiogenesis and neural activity. The MALAT1/miR-124-3p/EGR1 regulatory axis is partly responsible for retinal neovascularization, which may provide a novel theoretical basis for the pathogenesis of ROP.


Assuntos
Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , MicroRNAs/genética , Oxigênio/metabolismo , Animais , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/genética , RNA Longo não Codificante/genética , Retina/metabolismo , Neovascularização Retiniana/patologia
15.
Graefes Arch Clin Exp Ophthalmol ; 260(9): 2837-2846, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35438363

RESUMO

PURPOSE: To evaluate the retinal vascularization of repeated intravitreal ranibizumab (IVR) for reactivated retinopathy of prematurity (ROP) treated with IVR monotherapy. METHODS: The retrospective study reviewed ROP infants who accepted IVR injection as the first treatment in our department from January 2017 to December 2018. The ratio of the distance from the center of the optic disc to the border of the vascularized zone (DB) to the distance from the center of the disc to the fovea (DF) was used for the vascular outgrowth analysis. RESULTS: Seventy-eight infants were included in the study. A total of 54.3% of the reactivated ROP patients could achieve complete vascularization after repeated IVR injections. Gestational age (GA) > 29 weeks and a temporal DB/DF ratio ≥ 3 in the first IVR were potential predictors for complete retinal vascularization after IVR monotherapy. The temporal DB/DF ratio ≥ 3.6 in the second IVR injection was a potential predictor for complete retinal vascularization after repeated IVR for ROP reactivation. CONCLUSIONS: Reactivated ROP after IVR monotherapy can be treated successfully with repeated IVR injections. GA and temporal DB/DF ratio are potential predictors of complete retinal vascularization in ROP infants treated with IVR.


Assuntos
Neovascularização Retiniana , Retinopatia da Prematuridade , Inibidores da Angiogênese , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Injeções Intravítreas , Ranibizumab , Estudos Retrospectivos
16.
Retina ; 42(1): 55-63, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34393211

RESUMO

PURPOSE: To report the clinical features and surgical outcomes of encircling scleral buckling surgery with cryotherapy in familial exudative vitreoretinopathy (FEVR) patients with rhegmatogenous RD. METHODS: This study was a consecutive, retrospective interventional case series. Clinical features, including the FEVR stage, proliferative vitreoretinopathy grade, range of RD and degeneration, and presence of retinal breaks, and surgical outcomes, including the success rate, best-corrected visual acuity, and myopic shift, were analyzed. RESULTS: There were 16 eyes with Stage 3A FEVR and eight eyes with Stage 4A FEVR. 13 eyes had Grade A proliferative vitreoretinopathy, and 11 eyes had Grade B proliferative vitreoretinopathy. Retinal reattachment was achieved in 22 of 24 eyes (91.67%) with FEVR-rhegmatogenous RD after initial encircling scleral buckling surgery. The best-corrected visual acuity improved from a mean of 1.08 ± 0.86 logarithm of the minimum angle of resolution preoperatively to 0.45 ± 0.41 logarithm of the minimum angle of resolution postoperatively (P < 0.01). A myopic shift of -2.39 ± 1.38 (range, -1 to -6) diopter (P < 0.01) was observed. The mean follow-up period was 34.5 ± 27.7 (range, 7-104) months. CONCLUSION: Our study clarified the efficacy of encircling scleral buckling surgery with cryotherapy in FEVR-rhegmatogenous RD with Stage 3A or 4A FEVR and Grade A or B proliferative vitreoretinopathy, especially in patients with multiple retinal holes.


Assuntos
Crioterapia/métodos , Vitreorretinopatias Exsudativas Familiares/terapia , Descolamento Retiniano/etiologia , Recurvamento da Esclera/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Vitreorretinopatias Exsudativas Familiares/complicações , Vitreorretinopatias Exsudativas Familiares/diagnóstico , Feminino , Angiofluoresceinografia/métodos , Seguimentos , Fundo de Olho , Humanos , Masculino , Oftalmoscopia , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/terapia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
Retina ; 42(10): 1958-1964, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36018796

RESUMO

PURPOSE: To analyze the clinical features of LRP5 gene mutation-related familial exudative vitreoretinopathy and explore the potential phenotype-genotype correlation on LRP5 gene. METHODS: Eighty-seven familial exudative vitreoretinopathy (FEVR) families with LRP5 mutations were selected from 722 FEVR patients, which were divided into 2 groups, including 22 autosomal-recessive FEVR (ar-FEVR) families and 65 autosomal-dominant FEVR (ad-FEVR) families. Clinical and genetic data were retrospectively analyzed. The potential phenotype-genotype correlation was explored from the mutation type and inheritance pattern. RESULTS: No significant difference between the LRP5 null mutation subgroup and the LRP5 missense mutation subgroup was observed in the proportion of FEVR stage and the ratio of ocular involvement. Instead, a significant difference between the LRP5 ar-FEVR subgroup and the LRP5 ad-FEVR subgroup was observed in the proportion of FEVR stage and the ratio of binocularly severe phenotype. The probands with LRP5 gene recessive mutation showed a higher incidence of severe phenotype. Moreover, the ratio of binocularly severe patients in ar-FEVR was nearly 3.5 times higher than that in ad-FEVR. CONCLUSION: The severity of phenotype was more likely to be related to the synergistic effect of the variants.


Assuntos
Oftalmopatias Hereditárias , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Doenças Retinianas , Análise Mutacional de DNA , Oftalmopatias Hereditárias/epidemiologia , Oftalmopatias Hereditárias/genética , Vitreorretinopatias Exsudativas Familiares , Humanos , Incidência , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Mutação , Linhagem , Fenótipo , Doenças Retinianas/epidemiologia , Doenças Retinianas/genética , Estudos Retrospectivos
18.
Retina ; 42(2): 306-312, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35050929

RESUMO

PURPOSE: To report the long-term outcomes of lens capsular flap transplantation (LCFT) as initial treatment for large macular holes (MHs). METHODS: Thirteen consecutive eyes with large MHs who received LCFT as primary treatment were reviewed retrospectively. All enrolled eyes underwent standard 23-gauge vitrectomy, internal limiting membrane peeling, LCFT, and 15% perfluoropropane tamponade. Autologous whole blood was applied in selected eyes to make the LCT intact. A face-down position maintained for 2 weeks postoperatively. Data including demographic information, medical history, anatomical and functional outcomes, and complications were recorded. RESULTS: The mean preoperative MHs diameter was 979.42 ± 388.28 µm. Eight eyes received autologous LCFT, and the other five eyes received allogenic LCFT. Whole blood was applied in seven eyes. The mean follow-up duration was 19.57 ± 6.24 months (range: 12.0-32.2 months). The macular hole was successfully closed in all cases (13/13). The median best-corrected visual acuity improved from 1.76 (interquartile range, 1.23-1.91) logarithm of the minimum angle of resolution (median Snellen acuity: 20/1,150) preoperatively to 1.16 ± 0.47 logarithm of the minimum angle of resolution (mean Snellen acuity: 20/290) (P < 0.01) at the last visit. No severe complications were noted. CONCLUSION: Lens capsular flap transplantation may help to improve the closure rate and visual outcomes in large MHs, which could be an alternative method as primary treatment for large MHs.


Assuntos
Tamponamento Interno , Cápsula do Cristalino/transplante , Perfurações Retinianas/cirurgia , Retalhos Cirúrgicos/transplante , Vitrectomia , Idoso , Extração de Catarata , Criança , Feminino , Fluorocarbonos/administração & dosagem , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Decúbito Ventral , Perfurações Retinianas/diagnóstico por imagem , Perfurações Retinianas/fisiopatologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Transplante Autólogo , Resultado do Tratamento , Acuidade Visual/fisiologia
19.
BMC Ophthalmol ; 22(1): 329, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918671

RESUMO

PURPOSE: To describe and analyze the clinical prognosis of infants diagnosed of familial exudative vitreoretinopathy (FEVR) with single gene mutation in long-term follow-up. METHODS: A retrospective case study was conducted on 355 FEVR infants with single positive gene. RESULT: Of the 335 single-gene positive infant FEVR cases (under 3 years old), 20% (n = 67) was diagnosed of strabismus at first visit. Staging of various genotypes was different (P < 0.001). Patients with NDP mutations presented the most severe clinical phenotypes and patients with ZNF408 mutations presented the mildest clinical phenotypes. Most infants underwent surgery under 1 year old (5th stage 75 of 108 [69.44%]). The axial length of different genotypes showed no significant difference (P = 0.2891). The 1st to 3rd stage cases were given intravitreal injection and/or retina photocoagulation with the last follow-up vision above 20/67. The 4th to 5th stage cases received the transcorneal vitrectomy with lensectomy or lens sparing vitrectomy (LSV), whose lens maintained transparent after LSV (11/14[78.58%]). After 2 to 10 years of follow-up, 37.96% (41/108) of post-surgery cases showed retinal funnel-like unfold and posterior pole unfold, 69.57% (16/ 23) of which received second surgery for closure of pupil with good prognosis. At the last follow-up, 20% (60/300) were with vision above 20/200. CONCLUSION: LRP5 gene mutation was the most common mutation in FEVR patients. The severity of the clinical phenotype varied with different gene mutations. The main surgical methods for cases at Stage 4-5 were transcorneal vitrectomy with lensectomy or LSV. The earlier FEVR occurred, the worse prognosis would be. Active surgical intervention and lens sparing were necessary for cases at Stage 4-5.


Assuntos
Oftalmopatias Hereditárias , Doenças Retinianas , Proteínas de Ligação a DNA/genética , Vitreorretinopatias Exsudativas Familiares , Humanos , Mutação , Linhagem , Prognóstico , Doenças Retinianas/diagnóstico , Estudos Retrospectivos , Fatores de Transcrição/genética
20.
BMC Ophthalmol ; 22(1): 499, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36536320

RESUMO

PURPOSE: To investigate the efficacy of myopia control by comparing the orthokeratology (Ortho-K) treated eyes and the emmetropic contralateral eyes in unilateral myopic children, and to identify the inter-individual influence factors. METHOD: In this retrospective study, 1566 medical records of children wearing Ortho-K lens were reviewed, and 62 children who received monocular Ortho-K lens for more than 1 year were analyzed. The change in axial length (AL) of the Ortho-K eyes and the emmetropic contralateral eyes was recorded. To evaluate the absolute and relative efficacy of myopia control, the intra-bilateral absolute reduction in AL growth (ibARAL) and the intra-bilateral relative reduction in AL growth (ibRRAL) were calculated as main outcomes. Association of the AL elongation, ibARAL and ibRRAL with age, sex and ocular parameters was analyzed by correlation analysis and generalized estimating equation (GEE) analysis. RESULT: The average initial wearing age was 10.76 ± 1.45 (ranged 8.5 to 15.8). The average baseline SER was - 2.15 ± 1.03 (ranged - 5.25 to -1.00) D in the Ortho-K eyes and - 0.01 ± 0.40 (ranged - 0.75 to 0.75) D in the contralateral eyes. At the 1-year follow-up, the average increased AL was significantly less in the Ortho-K eyes (0.07 ± 0.18 mm) than in the fellow eyes (0.48 ± 0.24 mm) (p < 0.001). The mean ibARAL was 0.41 ± 0.30 mm, and the mean ibRRAL was 83.4%±56.3%. In the GEE model, the AL change in Ortho-K eyes (ß = 0.051, p = 0.009, 95%CI: 0.012 to 0.090), the ibARAL (ß= -0.153, p = 0.000, 95%CI: -0.228 to -0.078) and the ibRRAL (ß= -0.196, p = 0.020, 95%CI: -0.361 to -0.030) were independently associated with the spherical equivalent refraction (SER) of the Ortho-K eyes, after adjusting for age, sex, and keratometry. CONCLUSION: In our study, the Ortho-K treatment was efficacious in controlling axial length growth in the monocular orthokeratology treated unilateral myopic eyes. The efficacy increased when the myopia was more severe. In the children from 8 to 16 years old, the effectiveness was independent of age and sex.


Assuntos
Miopia , Procedimentos Ortoceratológicos , Humanos , Criança , Adolescente , Estudos Retrospectivos , Comprimento Axial do Olho , Miopia/terapia , Córnea , Refração Ocular
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