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1.
Diabetes Metab Res Rev ; 40(2): e3773, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38598767

RESUMO

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are proposed to alleviate the development of inflammatory eye diseases. However, the association between SGLT2i and retinal vascular occlusion remains unclear. Therefore, this study aims to explore the effects of SGLT2i on the incidence of retinal vascular occlusion. MATERIALS AND METHODS: This retrospective cohort study analysed electronic medical records data from the largest multi-institutional database in Taiwan. Individuals who initiated SGLT2is and dipeptidyl peptidase 4 inhibitors (DPP4is) between 2016 and 2019 were included in our analysis. To conduct a homogenous comparison, inverse probability of treatment weighting with propensity scoring was employed. The primary outcome was retinal vascular occlusion, and the secondary outcomes were retinal vascular occlusion-related complications (macular oedema, vitreous haemorrhage, and tractional retinal detachment) and conditions requiring vitreoretinal intervention (intravitreal injection, retinal laser therapy, and vitrectomy). RESULTS: In total, 12,074 SGLT2i users and 39,318 DPP4i users were included. The incidence rate of retinal vascular occlusion in the SGLT2i and DPP4i groups was 1.2 (95% confidence interval [CI], 0.9-1.4) and 1.6 (95% CI, 1.3-1.8) events per 1000 person-years, respectively, which yielded a subdistribution hazard ratio (SHR) of 0.74 (95% CI, 0.55-0.99). Similar risk reductions were observed in the retinal vascular occlusion-related complications (SHR, 0.76; 95% CI, 0.69-0.84) and conditions requiring vitreoretinal intervention (SHR, 0.84; 95% CI, 0.77-0.94). CONCLUSIONS: In this multi-institutional study in Taiwan, SGLT2i use was associated with a reduced risk of retinal vascular occlusion. Further prospective studies are required to ascertain this association.


Assuntos
Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Estudos Retrospectivos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Taiwan/epidemiologia
2.
Biotechnol Bioeng ; 121(7): 2163-2174, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38595326

RESUMO

Pathogenic bacterial membrane proteins (MPs) are a class of vaccine and antibiotic development targets with widespread clinical application. However, the inherent hydrophobicity of MPs poses a challenge to fold correctly in living cells. Herein, we present a comprehensive method to improve the soluble form of MP antigen by rationally designing multi-epitope chimeric antigen (ChA) and screening two classes of protein-assisting folding element. The study uses a homologous protein antigen as a functional scaffold to generate a ChA possessing four epitopes from transferrin-binding protein A of Glaesserella parasuis. Our engineered strain, which co-expresses P17 tagged-ChA and endogenous chaperones groEL-ES, yields a 0.346 g/L highly soluble ChA with the property of HPS-positive serum reaction. Moreover, the protein titer of ChA reaches 4.27 g/L with >90% soluble proportion in 5-L bioreactor, which is the highest titer reported so far. The results highlight a timely approach to design and improve the soluble expression of MP antigen in industrially viable applications.


Assuntos
Antígenos de Bactérias , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Reatores Biológicos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Escherichia coli/genética , Escherichia coli/metabolismo , Clostridiales/genética , Clostridiales/metabolismo , Solubilidade
3.
Retina ; 44(6): 1063-1072, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38346114

RESUMO

PURPOSE: To evaluate choroidal changes over time in school-age children with a history of prematurity. METHODS: A study of 416 eyes of 208 eligible participants, including 88, 190, 36, 56, and 46 eyes in the full-term control, preterm, spontaneously regressed retinopathy of prematurity, intravitreal bevacizumab (injection of bevacizumab)-treated retinopathy of prematurity, and laser-treated retinopathy of prematurity groups, respectively, were enrolled in this study. The choroidal thickness was measured 4 times at 6-month intervals using optical coherence tomography. RESULTS: Of all the groups, the laser-treated children had the thinnest choroid compared with full-term children (-52.3 µ m, P = 0.04). Preterm children exhibited greater attenuation in choroidal thickness over time than did full-term children (-6.3 ± 26.9 and -1.1 ± 12.8 µ m/year, P = 0.03), whereas no difference was observed between injection of bevacizumab and laser treatments (-4.6 ± 18.9 and -2.0 ± 15.7 µ m/year, P = 0.46). In all groups, the changes in axial length were negatively associated with the changes in choroidal thickness (all P < 0.05). CONCLUSION: A greater attenuation in choroid thickness over time was observed in preterm children than in full-term children, but this attenuation did not differ between injection of bevacizumab and laser treatments. Axial elongation was associated with choroidal thinning in school-age children.


Assuntos
Inibidores da Angiogênese , Bevacizumab , Corioide , Idade Gestacional , Injeções Intravítreas , Retinopatia da Prematuridade , Tomografia de Coerência Óptica , Humanos , Corioide/patologia , Corioide/diagnóstico por imagem , Estudos Prospectivos , Masculino , Tomografia de Coerência Óptica/métodos , Feminino , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Criança , Bevacizumab/administração & dosagem , Seguimentos , Recém-Nascido , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Recém-Nascido Prematuro , Fotocoagulação a Laser/métodos , Acuidade Visual
4.
Eye Contact Lens ; 50(2): 84-90, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38193846

RESUMO

OBJECTIVES: To determine the location and intensity of the corneal pigmented arc in orthokeratology (ortho-k)-treated children and its relationship with annual axial length (AL) change using Pentacam. METHODS: This retrospective cohort study enrolled children aged 9 to 15 years who had been followed up for at least one year after ortho-k treatment for myopia control. A Pentacam was used to determine the location and intensity of pigmented arc after lens wear. Annual AL changes were further used as the outcome measurement to determine their relationships with the location and intensity of pigmented arc using generalized estimating equations (GEE). RESULTS: In total, 62 eyes from 33 patients (mean age 10.9 years) were included in our final analysis. The mean follow-up time was 30.6 months. The mean annual AL changes were 0.10 mm. Age statistically correlated with annual AL change (GEE, P= 0.033). In addition, the annual AL change was negatively associated with the relative vertical distance of the lowest density of pigmented arc point based on the visual center, pupil center, and corneal thinnest point after adjustment with age ( P =0.005, P =0.004, and P< 0.001, respectively). CONCLUSIONS: Pentacam could be a useful tool for evaluating the location and intensity of the corneal pigmented arc. In addition, there was a negative correlation between the vertical distance of the pigmented arc and annual AL change. These findings may provide important information regarding myopia control, next-generation ortho-k design, and prescription.


Assuntos
Lentes de Contato , Miopia , Procedimentos Ortoceratológicos , Transtornos da Pigmentação , Criança , Humanos , Estudos Retrospectivos , Córnea , Miopia/terapia , Topografia da Córnea , Refração Ocular , Transtornos da Visão , Comprimento Axial do Olho
5.
Retina ; 43(11): 1945-1950, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37339455

RESUMO

BACKGROUND/PURPOSE: To evaluate clinical outcomes and assess genotype-phenotype correlations in patients with familial exudative vitreoretinopathy (FEVR). METHODS: Clinical charts of 40 patients with FEVR were reviewed. FEVR was staged per Pendergast and Trese, and retinal dragging and folds further classified per Yaguchi et al. We performed whole-exome sequencing and compared clinical characteristics between genetic-positive and genetic-negative groups. RESULTS: The mean duration of follow-up was 5.4 years (range: 0.33, 15) for genetic-positive and 6.9 (range: 1, 20) for genetic-negative patients. The mean age at diagnosis was 5.6 years (0.25, 27) for genetic-positive and 6.0 (0, 32) for genetic-negative patients. Genetic-positive patients reported 100% full-term births and genetic-negative patients reported 45% full-term births ( P = 0.0012). There were more patients with retinal folds with all major vessels affected (Yaguchi's Group 4) in genetic-positive compared with genetic-negative patients (21.4% vs. 2.6%, P = 0.045). TSPAN12 was the most common (57.1%) genetic mutation in our population of which 50% exhibited asymmetric presentation. CONCLUSION: Patients who test positive for a typical FEVR gene mutation reported more term births and had more severe disease by Yaguchi's classification. TSPAN12 was the most common genetic mutation in our population and had highly asymmetrical disease.


Assuntos
Oftalmopatias Hereditárias , Doenças Retinianas , Humanos , Vitreorretinopatias Exsudativas Familiares/diagnóstico , Centros de Atenção Terciária , Fenótipo , Tetraspaninas/genética , Linhagem , Doenças Retinianas/diagnóstico , Doenças Retinianas/genética , Mutação , Estudos de Associação Genética , Análise Mutacional de DNA , Oftalmopatias Hereditárias/genética
6.
Int J Mol Sci ; 24(6)2023 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-36982910

RESUMO

This study aims to investigate the outcomes and risk factors associated with poor vision (vision less than counting fingers, 2.0 logMAR, Snellen vision 20/2000) in patients with posterior or combined persistent fetal vasculature (PFV), with or without surgery. We retrospectively reviewed the medical records of patients who were diagnosed with PFV from January 2008 to April 2021. We included 51 eyes of 44 patients who presented with PFV, of which 38 eyes underwent surgical correction (pars plicata/plana vitrectomy, with or without lensectomy, and intraocular lens implantation) at the median age of 6.0 months (range: 0.7 to 82.0). The mean follow-up was 68.8 months ± 38.0 months. The axial length change in the eyes undergoing surgery was significantly higher than the eyes without surgery (p = 0.025). Initial anterior chamber collapse and retinal detachment were associated with poor vision (p = 0.006 and p = 0.002, respectively). In addition, 37% of eyes with posterior or combined PFV had vision better than counting fingers. Surgery for eyes with PFV could result in better eye growth. Visual outcomes remained poor and were associated with the level of macular abnormality. Initial anterior chamber collapse and retinal detachment at presentation were the risk factors for poor visual outcomes. Vitrectomy for selected PFV eyes is valuable and associated with a better cosmetic outcome (better eye growth).


Assuntos
Vítreo Primário Hiperplásico Persistente , Descolamento Retiniano , Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Estudos Retrospectivos , Vítreo Primário Hiperplásico Persistente/diagnóstico , Vítreo Primário Hiperplásico Persistente/cirurgia , Vitrectomia , Resultado do Tratamento , Complicações Pós-Operatórias
7.
Retina ; 42(7): 1330-1337, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35723921

RESUMO

PURPOSE: To compare between oral and intravenous (IV) ultrawide-field fluorescein angiography in pediatric patients with a history of prematurity of retinopathy or prematurity. METHODS: Pediatric patients (<18 year old; n = 107 patients) who underwent ultrawide-field fluorescein angiography for retinopathy of prematurity were categorized into oral and IV fluorescein angiography (FA) groups. Quality of FA images was graded on the order of retinal vessels visible. Reported outcomes were proportions of graded FA images, peak fluorescein intensity, and the time to first dye appearance and to reach peak fluorescence. RESULTS: Image quality analysis revealed that 91.5% of IV FA images had excellent image quality compared with only 55.6% of oral FA images (P < 0.01). There were still 83.3% of oral-contrast images with good or excellent image quality. The average time required for first dye appearance and peak fluorescence were significantly shorter in the IV FA group than in the oral FA group (P < 0.01). Peak intensity was greater in the IV group (141.41 ± 29.09) than in the oral group (111.25 ± 45.68; P < 0.01). Adverse reaction rates were similar between the two groups (P = 0.22). CONCLUSION: Ultrawide-field fluorescein angiography provides excellent-quality imaging of the retina in the pediatric population. Overall, oral FA is still an effective and useful alternative to IV FA in children with prematurity history.


Assuntos
Retinopatia da Prematuridade , Adolescente , Criança , Fluoresceína , Angiofluoresceinografia/métodos , Seguimentos , Humanos , Recém-Nascido , Vasos Retinianos , Retinopatia da Prematuridade/diagnóstico
8.
Retina ; 42(5): 967-972, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35125478

RESUMO

PURPOSE: To analyze the clinical characteristics, surgical outcomes, and risk factors associated with visual outcomes in patients with abusive head trauma (AHT). METHODS: We retrospectively reviewed surgical outcomes of patients with AHT who underwent vitrectomy from 2001 to 2019. The patients' demographics, comprehensive preoperative and postoperative ocular findings, surgical treatments, visual outcomes, and postoperative complications in the medical records were reviewed. Univariable and multivariable analyses were performed to identify the prognostic factors associated with visual outcomes. RESULTS: Fourteen children (18 eyes) diagnosed with AHT who underwent vitrectomy were evaluated. The most common surgical indication was vitreous hemorrhage (n = 6, 33%). Retinal attachment at the final visit was noted in 17 eyes (94%). Thirteen eyes (72%) had a best-corrected visual acuity less than 20/200 after vitrectomy. In the multivariable analysis, optic nerve atrophy (n = 9, 50%) was significantly associated with a poor visual prognosis (final best-corrected visual acuity worse than 20/200) after vitrectomy in children with AHT (95% confidence interval, 1.041-517.963, P = 0.0471). CONCLUSION: The general visual prognosis was poor for patients with AHT needing vitrectomy, although a high rate of retinal attachment was observed. Optic nerve atrophy is a prognostic factor for poor visual outcomes in patients with AHT who received ophthalmic surgery.


Assuntos
Traumatismos Craniocerebrais , Descolamento Retiniano , Atrofia , Criança , Traumatismos Craniocerebrais/complicações , Traumatismos Craniocerebrais/diagnóstico , Traumatismos Craniocerebrais/cirurgia , Humanos , Prognóstico , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual
9.
BMC Ophthalmol ; 22(1): 441, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36384460

RESUMO

BACKGROUND: Usher syndrome (USH) is an autosomal recessive disorder primarily responsible for deaf-blindness. Patients with subtype Usher syndrome type 1 (USH1) typically experience congenital sensorineural hearing loss, abnormal vestibular function, and retinitis pigmentosa (RP). Here we present a case of Usher syndrome type 1F (USH1F) with a novel homozygous variant in the calcium-dependent cell-cell adhesion protocadherin-15 (PCDH15) gene. CASE PRESENTATION: Ophthalmic examinations were evaluated over a course of 10 years and the disease-causing variant was identified by whole exome sequencing (WES). Initial and follow-up examination of color fundus photos after 10 years revealed an increase in bone spicule pigment deposits in both eyes. A parafoveal hyper-AF ring in both eyes was shown in fundus autofluorescence (FAF) with a progressive diameter-wise constriction observed over 8 years. Outer nuclear layer (ONL) loss was observed in parafoveal and perifoveal regions of both eyes on spectral domain-optical coherence tomography (SD-OCT). Full-field electroretinography (ffERG) showed extinguished global retinal function. WES identified a novel two-base-pair deletion, c.60_61del (p.Phe21Ter), in the PCDH15 gene, confirming the diagnosis of USH1F. CONCLUSIONS: We report a novel homozygous PCDH15 pathogenic variant expected to lead to nonsense-mediated decay (NMD) of PCDH15 mRNA. The patient exhibits a loss of function with USH1F, experiencing congenital hearing loss and syndromic RP.


Assuntos
Retinose Pigmentar , Síndromes de Usher , Humanos , Síndromes de Usher/diagnóstico , Síndromes de Usher/genética , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/genética , Retina , Caderinas/genética
10.
Int J Mol Sci ; 23(22)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36430677

RESUMO

Tissue inhibitors of metalloproteinases (TIMPs) play a crucial role in endogenous angiogenesis besides the regulation of matrix metalloproteinase (MMP) activity. Associations between TIMP-2 gene polymorphisms and the risk of retinopathy of prematurity (ROP) were examined. Premature infants born between 2009 and 2018 were included. Five single-nucleotide polymorphisms (SNPs) of TIMP-2 were analyzed with real-time polymerase chain reaction (PCR). Multivariate logistic regression was applied to model associations between TIMP-2 polymorphisms and ROP susceptibility and severity. The GA+AA genotype in individuals with the TIMP-2 polymorphism of rs12600817 was associated with a higher risk of ROP (odds ratio [OR]: 1.518, 95% confidence interval [CI]: 1.028-2.242) compared with their wild-type genotypes. The AA genotype (OR: 1.962, 95% CI: 1.023-3.762) and the AA+GA genotype (OR: 1.686, 95% CI: 1.030-2.762) in individuals with the rs12600817 polymorphism had higher risks of severe, treatment-requiring ROP relative to their wild-type counterparts. In patients with treatment-requiring ROP, the AG+GG genotypes in the TIMP-2 polymorphism of rs2889529 were correlated with the treatment response (p = 0.035). The TIMP-2 polymorphism of rs12600817 help in predicting ROP risks in preterm infants, while the polymorphism of rs2889529 can serve as a genetic marker in evaluating the ROP treatment response.


Assuntos
Retinopatia da Prematuridade , Inibidor Tecidual de Metaloproteinase-2 , Lactente , Humanos , Recém-Nascido , Inibidor Tecidual de Metaloproteinase-2/genética , Retinopatia da Prematuridade/genética , Retinopatia da Prematuridade/terapia , Recém-Nascido Prematuro , Polimorfismo de Nucleotídeo Único , Genótipo
11.
Int J Mol Sci ; 23(23)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36499293

RESUMO

Congenital stationary night blindness (CSNB) is an inherited retinal disease (IRD) that causes night blindness in childhood with heterogeneous genetic, electrophysical, and clinical characteristics. The development of sequencing technologies and gene therapy have increased the ease and urgency of diagnosing IRDs. This study describes seven Taiwanese patients from six unrelated families examined at a tertiary referral center, diagnosed with CSNB, and confirmed by genetic testing. Complete ophthalmic exams included best corrected visual acuity, retinal imaging, and an electroretinogram. The effects of identified novel variants were predicted using clinical details, protein prediction tools, and conservation scores. One patient had an autosomal dominant CSNB with a RHO variant; five patients had complete CSNB with variants in GRM6, TRPM1, and NYX; and one patient had incomplete CSNB with variants in CACNA1F. The patients had Riggs and Schubert-Bornschein types of CSNB with autosomal dominant, autosomal recessive, and X-linked inheritance patterns. This is the first report of CSNB patients in Taiwan with confirmed genetic testing, providing novel perspectives on molecular etiology and genotype-phenotype correlation of CSNB. Particularly, variants in TRPM1, NYX, and CACNA1F in our patient cohort have not previously been described, although their clinical significance needs further study. Additional study is needed for the genotype-phenotype correlation of different mutations causing CSNB. In addition to genetic etiology, the future of gene therapy for CSNB patients is reviewed and discussed.


Assuntos
Oftalmopatias Hereditárias , Doenças Genéticas Ligadas ao Cromossomo X , Miopia , Cegueira Noturna , Humanos , Oftalmopatias Hereditárias/genética , Oftalmopatias Hereditárias/terapia , Oftalmopatias Hereditárias/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Mutação , Miopia/diagnóstico , Miopia/genética , Miopia/terapia , Cegueira Noturna/diagnóstico , Cegueira Noturna/genética , Cegueira Noturna/terapia , Linhagem , Canais de Cátion TRPM/genética
12.
Hum Mutat ; 42(6): 641-666, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33847019

RESUMO

Cyclic nucleotide-gated channel ß1 (CNGB1) encodes the 240-kDa ß subunit of the rod photoreceptor cyclic nucleotide-gated ion channel. Disease-causing sequence variants in CNGB1 lead to autosomal recessive rod-cone dystrophy/retinitis pigmentosa (RP). We herein present a comprehensive review and analysis of all previously reported CNGB1 sequence variants, and add 22 novel variants, thereby enlarging the spectrum to 84 variants in total, including 24 missense variants (two of which may also affect splicing), 21 nonsense, 19 splicing defects (7 at noncanonical positions), 10 small deletions, 1 small insertion, 1 small insertion-deletion, 7 small duplications, and 1 gross deletion. According to the American College of Medical Genetics and Genomics classification criteria, 59 variants were considered pathogenic or likely pathogenic and 25 were variants of uncertain significance. In addition, we provide further phenotypic data from 34 CNGB1-related RP cases, which, overall, are in line with previous findings suggesting that this form of RP has long-term retention of useful central vision despite the early onset of night blindness, which is valuable for patient counseling, but also has implications for it being considered a priority target for gene therapy trials.


Assuntos
Distrofias de Cones e Bastonetes/genética , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Estudos de Coortes , Distrofias de Cones e Bastonetes/classificação , Distrofias de Cones e Bastonetes/epidemiologia , Distrofias de Cones e Bastonetes/patologia , Análise Mutacional de DNA , Estudos de Associação Genética , Humanos , Mutação
13.
Hum Mol Genet ; 28(20): 3475-3485, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31518400

RESUMO

Hypoxia associated with the high metabolic demand of rods has been implicated in the pathology of age-related macular degeneration (AMD), the most common cause of adult blindness in the developed world. The majority of AMD-associated severe vision loss cases are due to exudative AMD, characterized by neovascularization. To further investigate the causes and histopathology of exudative AMD, we conditionally induced hypoxia in a novel preclinical AMD model (Pde6gcreERT2/+;Vhl-/-) by targeting Vhl and used multimodal imaging and immunohistochemistry to track the development of hypoxia-induced neovascularization. In addition to developing a preclinical model that phenocopies exudative AMD, our studies revealed that the photoreceptor hypoxic response initiates and drives type 3 neovascularization, mainly in the outer retina. Activation of the VHL-HIF1a-VEGF-EPO pathway in the adult retina led to long-term neovascularization, retinal hemorrhages and compromised retinal layers. Our novel preclinical model would accelerate the testing of therapies that use metabolomic approaches to ameliorate AMD.


Assuntos
Hipóxia/metabolismo , Hipóxia/patologia , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Animais , Eritropoetina/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Fator A de Crescimento do Endotélio Vascular/metabolismo
14.
Exp Eye Res ; 202: 108352, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33166502

RESUMO

This study investigated the effects of growth factors and internal limiting membrane components on Müller cell migration. We studied the effects of epidermal growth factor (EGF), fibroblast growth factor (FGF), somatomedin (IGF-1), platelet derived growth factor (PDGF), and stromal cell-derived factor-1 alpha (SDF-1α) as well as collagen IV, laminin, and fibronectin on the proliferative and migratory activities of rat Müller cells in vitro. A water soluble tetrazolium-1 assay was used to quantify the viability of Müller cells in respective cultures, and analysis was performed using an enzyme-linked immunosorbent assay reader. All the factors examined had significant proliferative effects on cultured Müller cells (p < .05). A two-well Ibidi silicone culture insert was used to assess Müller cell migration. Müller cells cultured in EGF, FGF, IGF-1, collagen IV, and laminin but not in SDF, PDGF, or fibronectin effectively increased the cell migratory activity (p < .001). In addition, combined EGF and collagen IV, combined FGF and collagen IV, and combined IGF-1 and laminin exhibited more significant (p < .001) effects on Müller cell migration compared with culture a single factor. In summary, this study revealed the combinatorial effects of various growth factors and individual internal limiting membrane constituents. This may assist Müller cell migration together with the macular hole healing process.


Assuntos
Células Ependimogliais/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Perfurações Retinianas/metabolismo , Linhagem Celular , Movimento Celular , Células Ependimogliais/patologia , Humanos , Perfurações Retinianas/patologia
15.
BMC Ophthalmol ; 21(1): 68, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541298

RESUMO

BACKGROUND: To analyze multiple imaging modalities in patients with Bietti crystalline dystrophy (BCD) and to investigate which factors from these modalities are associated with best corrected visual acuity (BCVA). METHODS: In this retrospective study, 40 eyes from 22 patients with BCD were included and were separated into group 1 (BCVA ≤20/200) and group 2 (BCVA > 20/200). Data including BCVA and characteristic findings from near-infrared reflectance (NIR) imaging, fundus autofluorescence (FAF), and spectral domain-optic coherence tomography (SD-OCT) were analyzed and compared. The outcome measures of multimodal imaging were evaluated for correlation with BCVA. RESULTS: NIR is a good diagnostic tool for detecting either crystalline or sclerotic vessels in BCD. Patients in group 1 tended to have a thinner choroid (P = 0.047) with ellipsoid zone (EZ) disruption (P = 0.011). Calculation of the area under the curve indicated that EZ disruption detected on SD-OCT could be a good predictor of legal blindness in BCD. CONCLUSION: For the diagnosis of BCD, NIR could be a good diagnostic tool. Of the studied imaging modalities, we found that EZ disruption at the fovea were strongly associated with legal blindness, which could be easily assessed by SD-OCT.


Assuntos
Tomografia de Coerência Óptica , Distrofias Hereditárias da Córnea , Angiofluoresceinografia , Humanos , Doenças Retinianas , Estudos Retrospectivos , Acuidade Visual
16.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360834

RESUMO

Achromatopsia is characterized by amblyopia, photophobia, nystagmus, and color blindness. Previous animal models of achromatopsia have shown promising results using gene augmentation to restore cone function. However, the optimal therapeutic window to elicit recovery remains unknown. Here, we attempted two rounds of gene augmentation to generate recoverable mouse models of achromatopsia including a Cnga3 model with a knock-in stop cassette in intron 5 using Easi-CRISPR (Efficient additions with ssDNA inserts-CRISPR) and targeted embryonic stem (ES) cells. This model demonstrated that only 20% of CNGA3 levels in homozygotes derived from target ES cells remained, as compared to normal CNGA3 levels. Despite the low percentage of remaining protein, the knock-in mouse model continued to generate normal cone phototransduction. Our results showed that a small amount of normal CNGA3 protein is sufficient to form "functional" CNG channels and achieve physiological demand for proper cone phototransduction. Thus, it can be concluded that mutating the Cnga3 locus to disrupt the functional tetrameric CNG channels may ultimately require more potent STOP cassettes to generate a reversible achromatopsia mouse model. Our data also possess implications for future CNGA3-associated achromatopsia clinical trials, whereby restoration of only 20% functional CNGA3 protein may be sufficient to form functional CNG channels and thus rescue cone response.


Assuntos
Defeitos da Visão Cromática/genética , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Modelos Animais de Doenças , Edição de Genes , Mutação , Animais , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Defeitos da Visão Cromática/metabolismo , Técnicas de Introdução de Genes , Camundongos , Células Fotorreceptoras Retinianas Cones/metabolismo , Células Fotorreceptoras Retinianas Cones/fisiologia
17.
Mamm Genome ; 31(3-4): 77-85, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32342224

RESUMO

Retinitis pigmentosa (RP) is a neurodegenerative disorder that causes irreversible vision loss in over 1.5 million individuals world-wide. The genetic heterogeneity of RP necessitates a broad therapy that is able to provide treatment in a gene- and mutation- non-specific manner. In this study, we identify the therapeutic benefits of metabolic reprogramming by targeting pyruvate kinase M2 (PKM2) in a Pde6ß preclinical model of RP. The genetic contributions of PKM2 inhibition in retinal degeneration were evaluated through histology and electroretinogram (ERG) followed by a statistical analysis using a linear regression model. Notably, PKM2 ablation resulted in thicker retinal layers in Pde6ß-mutated mice as compared to the controls, suggesting greater photoreceptor survival. Consistent with these anatomical findings, ERG analyses revealed that the maximum b-wave is on average greater in Pkm2 knockout mice than in mice with intact Pkm2, indicating enhanced photoreceptor function. These rescue phenotypes from Pkm2 ablation in a preclinical model of RP indicate that a metabolome reprogramming may be useful in treating RP.


Assuntos
Piruvato Quinase/genética , Retina/patologia , Retinose Pigmentar/genética , Retinose Pigmentar/metabolismo , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Knockout , Mutação/genética , Degeneração Retiniana
18.
Graefes Arch Clin Exp Ophthalmol ; 258(7): 1367-1377, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32281001

RESUMO

PURPOSE: To evaluate prognostic factors in young patients with central retinal vein occlusion (CRVO). METHODS: Retrospective case series. CRVO patients aged ≤ 50 and follow-up ≥ 6 months were enrolled. The best corrected visual acuity (BCVA) and central retinal thickness (CRT) at baseline, 3 months, 6 months, and last visit were documented. Severity of retinopathy was graded by comparing to standard photos. Prognostic factors associated with visual outcome at 6 months were evaluated by multiple linear regression models. RESULTS: A total of 73 eyes from 69 patients with mean age 37.6 ± 8.5 were enrolled. Forty-seven (68%) patients were male. The mean follow-up duration was 25.9 ± 23.0 months. LogMAR BCVA improved from 0.979 ± 0.785 at baseline to 0.594 ± 0.748 at the 6 months (p < 0.001) and CRT improved from 475 ± 222 µm to 299 ± 104 µm (p < 0.001). Forty-eight (66%) eyes required anti-vascular endothelial growth factor (anti-VEGF) treatment. The mean number of injections was 2.25 ± 1.41 in the first 6 months and 75% of eyes received ≦ 3 injections during the clinical course. The baseline BCVA (coefficient 0.518, p < 0.001), grade of retinal hemorrhage (coefficient 0.230, p = 0.006), grade of retinal venous engorgement (coefficient 0.238, p = 0.011), grade of optic disc edema (coefficient - 0.226, p = 0.005), and diabetes mellitus (coefficient 0.264, p = 0.047) were the independent factors associated with visual outcome at 6 months. CONCLUSIONS: Baseline clinical features are useful for the prediction of visual outcome at 6 months in young CRVO patients.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Angiofluoresceinografia/métodos , Retina/patologia , Oclusão da Veia Retiniana/diagnóstico , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adolescente , Adulto , Feminino , Seguimentos , Fundo de Olho , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Oclusão da Veia Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/fisiopatologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto Jovem
19.
Retina ; 40(3): 572-580, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30531421

RESUMO

OBJECTIVE: This study aims to examine retinal vascular findings for affected eyes and contralateral eyes as well in typical cases of unilateral persistent fetal vasculature. METHODS: We retrospectively reviewed all patients evaluated at Chang Gung Memorial Hospital, Linkou, for unilateral persistent fetal vasculature between January 2008 and July 2017. All patients underwent fluorescein angiography (FA) examination under general anesthesia. FA was performed using RetCam 3 (Clarity Medical Systems, Inc, Pleasanton, CA). RESULTS: Ten patients (eight male and two female) were identified as having adequate clinical data for the final analysis. The mean age at diagnosis was 13.7 ± 17.2 months (range 1-58). The mean axial length was shorter in the affected eyes as compared to the fellow eyes (17.27 ± 2.8 vs. 20.2 ± 1.7 mm; P = 0.024). In the affected eyes, nine cases (90.0%) showed a concomitant retrolental stalk, avascular peripheral retina, regional capillary dropout, and absence of foveal avascular zone. Hyperfluorescent stalk was seen in seven cases (70.0%). Four eyes (40.0%) showed leaking vessels. Terminal supernumerary branching was seen in two cases (20.0%). Popcorn hyperfluorescence was noted in one case (10.0%). In the fellow eyes, peripheral avascular zone was noted in nine eyes (90.0%), of which six (60.0%) had peripheral zones greater than two-disk diameters. Seven eyes (70.0%) presented with regional capillary dropout and abnormal choroidal filling. Three eyes (30.0%) had abnormal vessel straightening. Aberrant circumferential vessels and leaking spots were seen in two eyes (20.0%). Regional dilation of disk vessels, peripheral vessel dilation, and terminal bulbing were noted in one eye (10.0%). The mean best-corrected visual acuity of the fellow eyes was 20/39 (0.29 in logarithm of the minimum angle of resolution). CONCLUSION: Retinal vascular abnormalities in the affected eyes and fundoscopically normal fellow eyes of unilateral persistent fetal vasculature patients were found in 100% and 90.0% of patients, respectively. Fellow eyes had some subtle abnormalities that were only revealed through FA. These unilateral persistent fetal vasculature cases were still bilaterally affected.


Assuntos
Corioide/irrigação sanguínea , Angiofluoresceinografia/métodos , Vítreo Primário Hiperplásico Persistente/diagnóstico , Vasos Retinianos/patologia , Pré-Escolar , Feminino , Fundo de Olho , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos
20.
Retina ; 40(9): 1793-1803, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31800460

RESUMO

PURPOSE: To determine the rates and risk factors of recurrent retinopathy of prematurity (ROP) treated by laser photocoagulation, intravitreal bevacizumab (IVB) monotherapy, or intravitreal ranibizumab (IVR) monotherapy. METHODS: In this retrospective cohort study, consecutive infants with Type 1 ROP who received laser, IVB, or IVR treatments were followed for at least 75 weeks of postmenstrual age. Data analysis was performed between March 2010 and February 2017 in Chang Gung Memorial Hospital, Linkou, Taiwan. RESULTS: A total of 176 infants (340 eyes) were included in this study. The mean follow-up was 197.3 ± 110 weeks. All of the baseline demographic and ROP characteristics among the laser, IVB, and IVR groups were similar. The overall recurrence rate after treatment was 44 of 340 eyes (12.9%). The IVB group had a recurrence rate of 10.0%, followed by the laser group (18.0%) and the IVR group (20.8%); however, these rates were not significantly different (P = 0.0528). Compared with the laser group, the IVB and IVR groups exhibited recurrence at later ages (43.4 ± 3.5 weeks for the IVB group, 42.3 ± 2.0 weeks for the IVR group, and 39.5 ± 2.8 weeks for the laser group; P = 0.0058). The mean interval of recurrence from initial treatment in the laser group was 3.6 ± 1.4 weeks compared with 8.8 ± 3.9 weeks and 8.3 ± 1.6 weeks in the IVB and IVR groups, respectively (P = 0.0001). Overall, the independent risk factors of recurrence included an early postmenstrual age at initial treatment (P = 0.0160), Zone I (P = 0.0007), low Apgar score (P = 0.0297), and multiple births (P = 0.0285). There was no significant difference in progression to retinal detachment among the three groups (laser: 3/61, 4.9%; IVB: 2/231, 0.9%;and IVR: 1/48, 2.1%; P = 0.2701). CONCLUSION: Laser, IVR, and IVB are effective for Type 1 ROP. Retinopathy of prematurity recurrence requiring re-treatment was encountered as late as 50 weeks of postmenstrual age after IVB or IVR but earlier after laser. Longer follow-up for infants treated with anti-vascular endothelial growth factor is needed, especially in patients with significant risk factors such as an early postmenstrual age at initial treatment, Zone I ROP, low Apgar score, and multiple births.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Fotocoagulação a Laser , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/epidemiologia , Bevacizumab/uso terapêutico , Peso ao Nascer , Feminino , Seguimentos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Injeções Intravítreas , Masculino , Oftalmoscopia , Ranibizumab/uso terapêutico , Recidiva , Retinopatia da Prematuridade/terapia , Estudos Retrospectivos , Fatores de Risco , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
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