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1.
Clin Exp Med ; 24(1): 98, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38727918

RESUMEN

The role of mast cells in physiologic and pathological processes extends far beyond the allergy processes: they are involved in wound healing, chronic inflammation, and tumor growth. This short article emphasizes the role played by mast cells in age-related macular degeneration (AMD). Mast cells can induce angiogenesis and are present around Bruch's membrane during the early and late stages of choroidal neovascularization in AMD. Proteolytic enzymes released by mast cells lead to thinning of the choroid in AMD as well as degradation of vascular basement membranes and Bruch's membrane, which in turn could result in retinal pigment epithelial death and choriocapillaris degeneration in geographical atrophy and exudative AMD.


Asunto(s)
Coroides , Degeneración Macular , Mastocitos , Humanos , Coroides/patología , Degeneración Macular/patología , Degeneración Macular/metabolismo , Neovascularización Coroidal/patología , Neovascularización Coroidal/metabolismo , Lámina Basal de la Coroides/patología , Lámina Basal de la Coroides/metabolismo
2.
J Biomed Sci ; 31(1): 48, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730462

RESUMEN

Retinal degenerative diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), loom as threats to vision, causing detrimental effects on the structure and function of the retina. Central to understanding these diseases, is the compromised state of the blood-retinal barrier (BRB), an effective barrier that regulates the influx of immune and inflammatory components. Whether BRB breakdown initiates retinal distress, or is a consequence of disease progression, remains enigmatic. Nevertheless, it is an indication of retinal dysfunction and potential vision loss.The intricate intercellular dialogues among retinal cell populations remain unintelligible in the complex retinal milieu, under conditions of inflammation and oxidative stress. The retina, a specialized neural tissue, sustains a ceaseless demand for oxygen and nutrients from two vascular networks. The BRB orchestrates the exchange of molecules and fluids within this specialized region, comprising the inner BRB (iBRB) and the outer BRB (oBRB). Extracellular vesicles (EVs) are small membranous structures, and act as messengers facilitating intercellular communication in this milieu.EVs, both from retinal and peripheral immune cells, increase complexity to BRB dysfunction in DR and AMD. Laden with bioactive cargoes, these EVs can modulate the retinal microenvironment, influencing disease progression. Our review delves into the multifaceted role of EVs in retinal degenerative diseases, elucidating the molecular crosstalk they orchestrate, and their microRNA (miRNA) content. By shedding light on these nanoscale messengers, from their biogenesis, release, to interaction and uptake by target cells, we aim to deepen the comprehension of BRB dysfunction and explore their therapeutic potential, therefore increasing our understanding of DR and AMD pathophysiology.


Asunto(s)
Barrera Hematorretinal , Vesículas Extracelulares , Barrera Hematorretinal/metabolismo , Barrera Hematorretinal/fisiopatología , Vesículas Extracelulares/metabolismo , Humanos , Retinopatía Diabética/fisiopatología , Retinopatía Diabética/metabolismo , Enfermedades de la Retina/fisiopatología , Enfermedades de la Retina/metabolismo , Degeneración Macular/fisiopatología , Degeneración Macular/metabolismo , Animales
3.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38732004

RESUMEN

Age-related macular degeneration (AMD) is an age-related disorder that is a global public health problem. The non-enzymatic Maillard reaction results in the formation of advanced glycation end products (AGEs). Accumulation of AGEs in drusen plays a key role in AMD. AGE-reducing drugs may contribute to the prevention and treatment of AGE-related disease. Fructosamine oxidase (FAOD) acts on fructosyl lysine and fructosyl valine. Based upon the published results of fructosamine 3-kinase (FN3K) and FAOD obtained in cataract and presbyopia, we studied ex vivo FAOD treatment as a non-invasive AMD therapy. On glycolaldehyde-treated porcine retinas, FAOD significantly reduced AGE autofluorescence (p = 0.001). FAOD treatment results in a breakdown of AGEs, as evidenced using UV fluorescence, near-infrared microspectroscopy on stained tissue sections of human retina, and gel permeation chromatography. Drusen are accumulations of AGEs that build up between Bruch's membrane and the retinal pigment epithelium. On microscopy slides of human retina affected by AMD, a significant reduction in drusen surface to 45 ± 21% was observed following FAOD treatment. Enzymatic digestion followed by mass spectrometry of fructose- and glucose-based AGEs (produced in vitro) revealed a broader spectrum of substrates for FAOD, as compared to FN3K, including the following: fructosyllysine, carboxymethyllysine, carboxyethyllysine, and imidazolone. In contrast to FN3K digestion, agmatine (4-aminobutyl-guanidine) was formed following FAOD treatment in vitro. The present study highlights the therapeutic potential of FAOD in AMD by repairing glycation-induced damage.


Asunto(s)
Productos Finales de Glicación Avanzada , Degeneración Macular , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/metabolismo , Degeneración Macular/patología , Humanos , Productos Finales de Glicación Avanzada/metabolismo , Animales , Porcinos , Retina/metabolismo , Retina/efectos de los fármacos , Retina/patología , Aminoácido Oxidorreductasas
4.
Sci Rep ; 14(1): 11016, 2024 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745035

RESUMEN

The aim of this study is to assess the relationship between dietary intake of fatty acids and the age-related macular degeneration (AMD) in the United States population. Adult participants of the 2005-2008 National Health and Nutrition Examination Survey (NHANES) were included in this nationwide cross-sectional study. Dietary fatty acid intake was obtained from two 24-h dietary recall interviews. The intake of dietary fatty acids was analyzed as a continuous and categorical variable. AMD status was assessed using nonmydriatic fundus photographs. Univariate and multivariate logistic regression analyses were used to assess the association between dietary fatty acid intake and AMD. The unweighted population included 4702 individuals of whom 374 had AMD. After adjusting for relevant variables, each 1 unit increase (1 mg/1000 kcal) intake of EPA (OR: 0.996, 95% CI: 0.993-0.996, P = 0.018), DPA (OR: 0.976, 95% CI: 0.962-0.990, P = 0.002), and DHA (OR: 0.996, 95% CI: 0.994-0.999, P = 0.003) were significantly decreased odds of any AMD. The highest versus lowest quartile of EPA (OR: 0.476, P for trend < 0.001), DPA (OR: 0.467, P for trend = 0.005) and DHA (OR: 0.586, P for trend = 0.008) were negatively associated with the odds of any AMD. Subgroup analysis showed that higher quartiles of EPA (OR: 0.461, P for trend < 0.002), DPA (OR: 0.467, P for trend = 0.006) and DHA (OR: 0.578, P for trend = 0.007) exhibited a negative association with early AMD. The study found no significant association between the intake of dietary fatty acids, including n-3 PUFA, and the odds of late AMD. In the 2005-2008 NHANES population, higher dietary DHA, DPA and EPA intake associated with decreased odds of early AMD. However, no clear association was found between specific types of FAs and late AMD.


Asunto(s)
Ácidos Grasos , Degeneración Macular , Encuestas Nutricionales , Humanos , Degeneración Macular/epidemiología , Degeneración Macular/etiología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Transversales , Ácidos Grasos/administración & dosificación , Estados Unidos/epidemiología , Grasas de la Dieta/administración & dosificación , Adulto , Dieta , Ácido Eicosapentaenoico/administración & dosificación
5.
Invest Ophthalmol Vis Sci ; 65(5): 17, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38717424

RESUMEN

Purpose: We aimed to identify structural differences in normal eyes, early age-related macular degeneration (AMD), and intermediate AMD eyes using optical coherence tomography (OCT) in a well-characterized, large cross-sectional cohort. Methods: Subjects ≥ 60 years with healthy normal eyes, as well as early or intermediate AMD were enrolled in the Alabama Study on Age-related Macular Degeneration 2 (ALSTAR2; NCT04112667). Using Spectralis HRA + OCT2, we obtained macular volumes for each participant. An auto-segmentation software was used to segment six layers and sublayers: photoreceptor inner and outer segments, subretinal drusenoid deposits (SDDs), retinal pigment epithelium + basal lamina (RPE + BL), drusen, and choroid. After manually refining the segmentations of all B-scans, mean thicknesses in whole, central, inner and outer rings of the ETDRS grid were calculated and compared among groups. Results: This study involved 502 patients, 252 were healthy, 147 had early AMD, and 103 had intermediate AMD eyes (per Age-Related Eye Disease Study [AREDS] 9-step). Intermediate AMD eyes exhibited thicker SDD and drusen, thinner photoreceptor inner segments, and RPE compared to healthy and early AMD eyes. They also had thicker photoreceptor outer segments than early AMD eyes. Early AMD eyes had thinner photoreceptor outer segments than normal eyes but a thicker choroid than intermediate AMD eyes. Using the Beckman scale, 42% of the eyes initially classified as early AMD shifted to intermediate AMD, making thickness differences for photoreceptor outer segments and choroid insignificant. Conclusions: With AMD stages, the most consistent structural differences involve appearance of drusen and SDD, followed by RPE + BL thickness, and then thickness of photoreceptor inner and outer segments. Structural changes in the transition from aging to intermediate AMD include alterations in the outer retinal bands, including the appearance of deposits on either side of the RPE.


Asunto(s)
Coroides , Degeneración Macular , Drusas Retinianas , Epitelio Pigmentado de la Retina , Tomografía de Coherencia Óptica , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Coroides/patología , Coroides/diagnóstico por imagen , Estudios Transversales , Degeneración Macular/diagnóstico , Drusas Retinianas/diagnóstico , Segmento Externo de las Células Fotorreceptoras Retinianas/patología , Epitelio Pigmentado de la Retina/patología , Epitelio Pigmentado de la Retina/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Agudeza Visual/fisiología
6.
Invest Ophthalmol Vis Sci ; 65(5): 16, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38717425

RESUMEN

Purpose: Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD. Methods: Adults ≥ 70 years with normal retinal aging, early AMD, or intermediate AMD per Age-Related Eye Disease Study (AREDS) nine-step grading of color fundus photography were enrolled in a cross-sectional study. Optical coherence tomography (OCT) volumes underwent 11-line segmentation and adjustments by a trained operator. Evaluated thicknesses reflect the vertical organization of retinal neurons and two vascular watersheds: NFL, ganglion cell layer-inner plexiform layer complex (GCL-IPL), inner retina, outer retina (including retinal pigment epithelium-Bruch's membrane), and total retina. Thicknesses were area weighted to achieve mean thickness across the 6-mm-diameter Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. Cognitive status was assessed by the National Institutes of Health Toolbox cognitive battery for fluid and crystallized cognition. Correlations estimated associations between cognition and thicknesses, adjusting for age. Results: Based on 63 subjects (21 per group), thinning of the outer retina was significantly correlated with lower cognition scores (P < 0.05). No other retinal thickness variables were associated with cognition. Conclusions: Only the outer retina (photoreceptors, supporting glia, retinal pigment epithelium, Bruch's membrane) is associated with cognition in aging to intermediate AMD; NFL was not associated with cognition, contrary to AD-associated condition reports. Early and intermediate AMD constitute a retinal disease whose earliest, primary impact is in the outer retina. Our findings hint at a unique impact on the brain from the outer retina in persons with AMD.


Asunto(s)
Envejecimiento , Cognición , Degeneración Macular , Retina , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Masculino , Anciano , Femenino , Estudios Transversales , Envejecimiento/fisiología , Anciano de 80 o más Años , Degeneración Macular/fisiopatología , Cognición/fisiología , Retina/diagnóstico por imagen , Retina/patología , Retina/fisiopatología , Fibras Nerviosas/patología , Células Ganglionares de la Retina/patología
7.
Arch. Soc. Esp. Oftalmol ; 99(5): 195-204, May. 2024. tab, ilus
Artículo en Español | IBECS | ID: ibc-VR-70

RESUMEN

La degeneración macular asociada a la edad (DMAE) constituye una de las principales causas de la pérdida de agudeza visual (AV) en los mayores de 50 años en el mundo, siendo la DMAE neovascular (DMAEn) la causante del 80% de los casos de pérdida de visión severa debido a esta enfermedad. Hace ya más de una década que se emplean los fármacos antifactor de crecimiento del endotelio vascular (anti-VEGF) para el tratamiento de esta enfermedad, cambiando drásticamente el pronóstico visual de estos pacientes. Sin embargo, los primeros estudios de los que se disponían datos de los resultados eran a corto plazo. En la actualidad existen ya diferentes series publicadas de los resultados de la DMAE a largo plazo tras el tratamiento con anti-VEGF, siendo el objetivo de la presente revisión sintetizar dichos resultados. El seguimiento medio de los estudios incluidos fue de 8,2 años (rango: 5-12 años). La AV inicial media fue 55,3 letras del Early Treatment Diabetic Retinopathy Study (ETDRS) (rango: 45,6-65) siendo la AV final media 50,1 letras (rango: 33,0-64,3), existiendo una pérdida media de 5,2 letras. Al final del seguimiento un 29,4% de los pacientes mantuvieron una AV>70 letras. El 67,9% de los pacientes se mantuvo estable al final del seguimiento (<15 letras de pérdida), existiendo una pérdida severa (≥15 letras) del 30,1%. La fibrosis y la atrofia fueron las principales causas de pérdida de AV a largo plazo, presentándose al final del seguimiento en un 52,5% y un 60,5%, respectivamente.(AU)


Age-related macular degeneration (AMD) is one of the main causes of visual acuity (VA) loss in people over 50 years of age worldwide, with neovascular AMD (nAMD) accounting for 80% of cases of severe vision loss due to this disease. Anti-vascular endothelial growth factor (anti-VEGF) drugs have been used for the treatment of this disease for more than a decade, changing drastically the visual prognosis of these patients. However, initial studies reporting data on outcomes were short term. Currently, there are different series published on the long-term results of AMD after treatment with anti-VEGF, and the aim of this review is to synthesize these results. The mean follow-up of the included studies was 8.2 years (range 5-12 years). The mean initial VA was 55.3 letters in the Early Treatment Diabetic Retinopathy Study (ETDRS) (range 45.6-65) and the mean final VA was 50.1 letters (range 33.0-64.3), with a mean loss of 5.2 letters. At the end of follow-up, 29.4% of the patients maintained a VA>70 letters. The 67.9% of patients remained stable at the end of follow-up (<15 letter loss), with a severe loss (≥15 letters) of 30.1%. Fibrosis and atrophy were the main causes of long-term VA loss, occurring at the end of follow-up in 52.5% and 60.5%, respectively.(AU)


Asunto(s)
Humanos , Masculino , Femenino , Niño , Degeneración Macular , Inhibidores de la Angiogénesis , Pronóstico , Membrana Epirretinal , Oftalmología , Oftalmopatías
8.
Arch. Soc. Esp. Oftalmol ; 99(5): 205-208, May. 2024. tab, ilus
Artículo en Español | IBECS | ID: ibc-VR-71

RESUMEN

El síndrome de Bardet-Biedl (SBB) es una ciliopatía que se asocia principalmente a distrofia retiniana, disfunción renal, polidactilia posaxial, obesidad, déficit cognitivo e hipogonadismo. Los síntomas vinculados a la distrofia retiniana no suelen aparecer hasta la primera década de vida, por lo que la detección tiende a retrasarse. La afectación ocular puede ser la forma inicial de manifestación de este síndrome, incluso puede ser la única, por lo que se debería tener en cuenta en el diagnóstico diferencial de una ambliopía en un niño que no mejora a pesar del correcto cumplimiento del tratamiento. Se presenta un caso de baja agudeza visual (AV) en una paciente pediátrica como manifestación inicial que lleva al diagnóstico del SBB y que es, además, el único síntoma que exhibe hasta la fecha, a pesar de tratarse de una enfermedad multisistémica.(AU)


Bardet–Biedl syndrome is a ciliopathy mainly associated with retinal dystrophy, renal dysfunction, post-axial polydactyly, obesity, cognitive deficit and hypogonadism. The symptoms associated with retinal dystrophy do not usually appear until the first decade of life, so the diagnosis is usually delayed. Ocular involvement may be the initial form of manifestation of this syndrome, it may even be the only one, so it should be taken into account in the differential diagnosis of amblyopia in a child who does not improve despite correct compliance with treatment. A case of low visual acuity in a pediatric patient is presented as an initial manifestation that leads to the diagnosis of Bardet–Biedl syndrome, and which is also the only symptom that the patient presents to date, despite being a multisystem disease.(AU)


Asunto(s)
Humanos , Femenino , Síndrome de Bardet-Biedl , Oftalmopatías , Visión Ocular , Degeneración Macular , Ambliopía , Distrofias Retinianas , Pacientes Internos , Examen Físico , Oftalmología
9.
Arch. Soc. Esp. Oftalmol ; 99(5): 218-221, May. 2024. ilus
Artículo en Español | IBECS | ID: ibc-VR-74

RESUMEN

El síndrome de Sneddon (SS) se manifiesta por múltiples accidentes cerebrovasculares y livedo reticularis. La vasculopatía livedoide (VL) se caracteriza por una larga historia de ulceración de pies y piernas y una histopatología que indica un proceso trombótico. Se describe una oclusión de rama arterial retiniana en un varón de 52años con VL. No presentó anomalías de laboratorio perceptibles, como anticuerpos antifosfolípidos, ni antecedentes de accidentes cerebrovasculares. La oclusión de arteria retiniana acompañada de VL podría ser una variante del síndrome de Sneddon. Con angiografía por tomografía de coherencia óptica se observó en la mácula en el ojo asintomático una reducción de las capas vasculares, lo que indica cambios microvasculares localizados como marcador evolutivo en la patogénesis del SS.(AU)


Sneddon's syndrome (SS) manifests through multiple strokes and livedo reticularis. Livedoid vasculopathy (LV) is characterized by a long history of foot and leg ulceration and histopathology indicating a thrombotic process. Arterial retinal branch occlusion is described in a 52-year-old male with LV. He did not present noticeable laboratory abnormalities, such as antiphospholipid antibodies, or a history of strokes. Retinal artery occlusion accompanied by LV could be a variant of Sneddon's syndrome. Optical coherence tomography angiography revealed a reduction in the macula's vascular layers in the asymptomatic eye, indicating localized microvascular changes as an evolving marker in the pathogenesis of SS.(AU)


Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Síndrome de Sneddon , Oclusión de la Arteria Retiniana , Degeneración Macular , Tomografía de Coherencia Óptica , Oftalmología , Oftalmopatías , Pacientes Internos , Examen Físico
10.
Invest Ophthalmol Vis Sci ; 65(5): 9, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38700873

RESUMEN

Purpose: We sought to explore whether sex imbalances are discernible in several autosomally inherited macular dystrophies. Methods: We searched the electronic patient records of our large inherited retinal disease cohort, quantifying numbers of males and females with the more common (non-ABCA4) inherited macular dystrophies (associated with BEST1, EFEMP1, PROM1, PRPH2, RP1L1, and TIMP3). BEST1 cases were subdivided into typical autosomal dominant and recessive disease. For PRPH2, only patients with variants at codons 172 or 142 were included. Recessive PROM1 and recessive RP1L1 cases were excluded because these variants give a more widespread or peripheral degeneration. The proportion of females was calculated for each condition; two-tailed binomial testing was performed. Where a significant imbalance was found, previously published cohorts were also explored. Results: Of 325 patients included, numbers for BEST1, EFEMP1, PROM1, PRPH2, RP1L1, and TIMP3 were 152, 35, 30, 50, 14, and 44, respectively. For autosomal dominant Best disease (n = 115), there were fewer females (38%; 95% confidence interval [CI], 29-48%; P = 0.015). For EFEMP1-associated disease (n = 35), there were significantly more females (77%; 95% CI, 60%-90%; P = 0.0019). No significant imbalances were seen for the other genes. When pooling our cohort with previous large dominant Best disease cohorts, the proportion of females was 37% (95% CI, 31%-43%; P = 1.2 × 10-5). Pooling previously published EFEMP1-cases with ours yielded an overall female proportion of 62% (95% CI, 54%-69%; P = 0.0023). Conclusions: This exploratory study found significant sex imbalances in two autosomal macular dystrophies, suggesting that sex could be a modifier. Our findings invite replication in further cohorts and the investigation of potential mechanisms.


Asunto(s)
Degeneración Macular , Humanos , Femenino , Masculino , Distribución por Sexo , Degeneración Macular/genética , Degeneración Macular/diagnóstico , Proteínas de la Matriz Extracelular/genética , Proteínas del Ojo/genética , Periferinas/genética , Inhibidor Tisular de Metaloproteinasa-3/genética
11.
Med Sci Monit ; 30: e943140, 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38702879

RESUMEN

BACKGROUND Age-related macular degeneration (AMD) is the most common cause of visual impairment in the elderly population in industrialized countries. The Study of Health in Pomerania (SHIP) with its cohort SHIP-TREND was designed to investigate risk factors and clinical disorders in the general population of northeast Germany. This work focused on the first follow-up of SHIP-TREND and determined associated modifiable risk factors of AMD. Modifying risk factors is important to slow the progression of early AMD as there is currently no treatment for the late stage of geographic atrophy. Understanding AMD-associated risk factors also plays an important role in the development of therapeutic concepts. MATERIAL AND METHODS Between 2016 and 2019, data were collected from a total of 2507 initially randomly selected subjects from the general population aged 28 to 89 years. Non-mydriatic fundus photography of the right eye was performed in 2489 subjects. Grading of AMD was performed using the Rotterdam classification system. RESULTS We included 1418 gradable fundus photographs in the analysis. The risk of AMD changes increased with age and was positively correlated with HDL cholesterol, fT3, and low educational level. In men, BMI and cigarette smoking were also positively associated with AMD changes. CONCLUSIONS This study emphasizes the consideration of various metabolic pathways for the development of therapeutic concepts.


Asunto(s)
Degeneración Macular , Humanos , Degeneración Macular/epidemiología , Masculino , Anciano , Factores de Riesgo , Femenino , Alemania/epidemiología , Persona de Mediana Edad , Anciano de 80 o más Años , Adulto , Estudios de Cohortes
12.
Sci Rep ; 14(1): 10044, 2024 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-38698112

RESUMEN

Clinical studies using suspensions or sheets of human pluripotent cell-derived retinal pigment epithelial cells (hiPSC-RPE) have been conducted globally for diseases such as age-related macular degeneration. Despite being minimally invasive, cell suspension transplantation faces challenges in targeted cell delivery and frequent cell leakage. Conversely, although the RPE sheet ensures targeted delivery with correct cell polarity, it requires invasive surgery, and graft preparation is time-consuming. We previously reported hiPSC-RPE strips as a form of quick cell aggregate that allows for reliable cell delivery to the target area with minimal invasiveness. In this study, we used a microsecond pulse laser to create a local RPE ablation model in cynomolgus monkey eyes. The hiPSC-RPE strips were transplanted into the RPE-ablated and intact sites. The hiPSC-RPE strip stably survived in all transplanted monkey eyes. The expansion area of the RPE from the engrafted strip was larger at the RPE injury site than at the intact site with no tumorigenic growth. Histological observation showed a monolayer expansion of the transplanted RPE cells with the expression of MERTK apically and collagen type 4 basally. The hiPSC-RPE strip is considered a beneficial transplantation option for RPE cell therapy.


Asunto(s)
Células Madre Pluripotentes Inducidas , Macaca fascicularis , Epitelio Pigmentado de la Retina , Animales , Epitelio Pigmentado de la Retina/trasplante , Epitelio Pigmentado de la Retina/citología , Humanos , Células Madre Pluripotentes Inducidas/citología , Degeneración Macular/patología
13.
Nat Commun ; 15(1): 3780, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38710714

RESUMEN

Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.


Asunto(s)
Neovascularización Coroidal , Dependovirus , Terapia Genética , Vectores Genéticos , Epitelio Pigmentado de la Retina , Animales , Dependovirus/genética , Vectores Genéticos/genética , Vectores Genéticos/administración & dosificación , Terapia Genética/métodos , Ratones , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/virología , Neovascularización Coroidal/terapia , Neovascularización Coroidal/genética , Conejos , Humanos , Técnicas de Transferencia de Gen , Degeneración Macular/terapia , Degeneración Macular/genética , Degeneración Macular/patología , Modelos Animales de Enfermedad , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Transducción Genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ratones Endogámicos C57BL , Retina/metabolismo , Retina/virología , Masculino , Células HEK293
14.
Front Immunol ; 15: 1366841, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38711521

RESUMEN

Introduction: Age-related macular degeneration (AMD) is a prevalent, chronic and progressive retinal degenerative disease characterized by an inflammatory response mediated by activated microglia accumulating in the retina. In this study, we demonstrate the therapeutically effects and the underlying mechanisms of microglial repopulation in the laser-induced choroidal neovascularization (CNV) model of exudative AMD. Methods: The CSF1R inhibitor PLX3397 was used to establish a treatment paradigm for microglial repopulation in the retina. Neovascular leakage and neovascular area were examined by fundus fluorescein angiography (FFA) and immunostaining of whole-mount RPE-choroid-sclera complexes in CNV mice receiving PLX3397. Altered cellular senescence was measured by beta-galactosidase (SA-ß-gal) activity and p16INK4a expression. The effect and mechanisms of repopulated microglia on leukocyte infiltration and the inflammatory response in CNV lesions were analyzed. Results: We showed that ten days of the CSF1R inhibitor PLX3397 treatment followed by 11 days of drug withdrawal was sufficient to stimulate rapid repopulation of the retina with new microglia. Microglial repopulation attenuated pathological choroid neovascularization and dampened cellular senescence in CNV lesions. Repopulating microglia exhibited lower levels of activation markers, enhanced phagocytic function and produced fewer cytokines involved in the immune response, thereby ameliorating leukocyte infiltration and attenuating the inflammatory response in CNV lesions. Discussion: The microglial repopulation described herein are therefore a promising strategy for restricting inflammation and choroidal neovascularization, which are important players in the pathophysiology of AMD.


Asunto(s)
Aminopiridinas , Neovascularización Coroidal , Modelos Animales de Enfermedad , Microglía , Animales , Neovascularización Coroidal/etiología , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/metabolismo , Neovascularización Coroidal/patología , Microglía/metabolismo , Microglía/efectos de los fármacos , Ratones , Aminopiridinas/farmacología , Aminopiridinas/uso terapéutico , Ratones Endogámicos C57BL , Degeneración Macular/patología , Degeneración Macular/metabolismo , Degeneración Macular/tratamiento farmacológico , Inflamación , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/antagonistas & inhibidores , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Pirroles/farmacología , Pirroles/uso terapéutico , Senescencia Celular/efectos de los fármacos
15.
J Clin Invest ; 134(9)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38690727

RESUMEN

Careful regulation of the complement system is critical for enabling complement proteins to titrate immune defense while also preventing collateral tissue damage from poorly controlled inflammation. In the eye, this balance between complement activity and inhibition is crucial, as a low level of basal complement activity is necessary to support ocular immune privilege, a prerequisite for maintaining vision. Dysregulated complement activation contributes to parainflammation, a low level of inflammation triggered by cellular damage that functions to reestablish homeostasis, or outright inflammation that disrupts the visual axis. Complement dysregulation has been implicated in many ocular diseases, including glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD). In the last two decades, complement activity has been the focus of intense investigation in AMD pathogenesis, leading to the development of novel therapeutics for the treatment of atrophic AMD. This Review outlines recent advances and challenges, highlighting therapeutic approaches that have advanced to clinical trials, as well as providing a general overview of the complement system in the posterior segment of the eye and selected ocular diseases.


Asunto(s)
Activación de Complemento , Proteínas del Sistema Complemento , Degeneración Macular , Humanos , Degeneración Macular/inmunología , Degeneración Macular/patología , Proteínas del Sistema Complemento/inmunología , Proteínas del Sistema Complemento/metabolismo , Activación de Complemento/inmunología , Animales , Ojo/inmunología , Ojo/patología
16.
Nutrients ; 16(9)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38732522

RESUMEN

This study assessed the prevalence of myopia, cataracts, glaucoma, and macular degeneration among Koreans over 40, utilizing data from the 7th Korea National Health and Nutrition Examination Survey (KNHANES VII, 2018). We analyzed 204,973 adults (44% men, 56% women; mean age 58.70 ± 10.75 years), exploring the association between myopia and these eye diseases through multivariate logistic regression, adjusting for confounders and calculating adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results showed a myopia prevalence of 44.6%, cataracts at 19.4%, macular degeneration at 16.2%, and glaucoma at 2.3%, with significant differences across ages and genders. A potential link was found between myopia and an increased risk of cataracts and macular degeneration, but not with glaucoma. Additionally, a higher dietary intake of carbohydrates, polyunsaturated and n-6 fatty acids, vitamins, and minerals correlated with lower risks of these diseases, underscoring the importance of the diet in managing and preventing age-related eye conditions. These findings highlight the need for dietary considerations in public health strategies and confirm myopia as a significant risk factor for specific eye diseases in the aging Korean population.


Asunto(s)
Catarata , Dieta , Degeneración Macular , Miopía , Encuestas Nutricionales , Humanos , Masculino , Femenino , República de Corea/epidemiología , Persona de Mediana Edad , Estudios Transversales , Miopía/epidemiología , Miopía/etiología , Anciano , Prevalencia , Degeneración Macular/epidemiología , Degeneración Macular/etiología , Adulto , Factores de Riesgo , Catarata/epidemiología , Catarata/etiología , Dieta/estadística & datos numéricos , Dieta/efectos adversos , Oftalmopatías/epidemiología , Oftalmopatías/etiología , Glaucoma/epidemiología , Glaucoma/etiología , Oportunidad Relativa , Nutrientes
17.
Vestn Oftalmol ; 140(2. Vyp. 2): 7-15, 2024.
Artículo en Ruso | MEDLINE | ID: mdl-38739125

RESUMEN

PURPOSE: This study compares the changes in the parameters of the anterior chamber of the eye using anterior segment optical coherence tomography (AS-OCT) in patients with a natural and artificial lens after treatment of neovascular age-related macular degeneration (nAMD) by multiple intravitreal injections (IVI) of anti-VEGF drugs. MATERIAL AND METHODS: The patients were divided into 2 groups: group 1 (control) included 30 patients (30 eyes) with a natural lens, group 2 - 30 patients (30 eyes) with an intraocular lens (IOL). AS-OCT was performed using the Revo NX tomograph (Optopol, Poland) to analyze anterior chamber depth (ACD) and the parameters of anterior chamber angle (ACA). Intraocular pressure (IOP) was measured with a contact tonometer ICare Pro. RESULTS: In patients with an IOL, the IOP level 1 minute after intravitreal injection (IVI) of an anti-VEGF drug was statistically lower than in the control group, on average by 17.8% during the first IVI and by 28.7% after 1 year of observation (p<0.001). ACD before treatment was statistically significantly higher in patients with IOL compared to patients of group 1 by an average of 39.3% (p<0.001). ACA from the nasal and temporal sides in the meridian 0°-180° before the start of treatment was statistically significantly wider in phakic patients than in the control group, by an average of 15.9±9.3° (p<0.001) and 16.9±8.2° (p<0.001), respectively. According to AS-OCT, there was no shift of the iris-lens diaphragm in patients with an IOL after multiple IVI of an anti-VEGF drug, in contrast to the control group. CONCLUSIONS: AS-OCT was used to determine for the first time the changes in the parameters of the anterior chamber of the eye in patients with a natural and artificial lens after multiple injections of an anti-VEGF drug in the treatment of nAMD.


Asunto(s)
Inhibidores de la Angiogénesis , Biometría , Presión Intraocular , Inyecciones Intravítreas , Tomografía de Coherencia Óptica , Humanos , Masculino , Presión Intraocular/efectos de los fármacos , Presión Intraocular/fisiología , Femenino , Tomografía de Coherencia Óptica/métodos , Anciano , Biometría/métodos , Inhibidores de la Angiogénesis/administración & dosificación , Segmento Anterior del Ojo/diagnóstico por imagen , Segmento Anterior del Ojo/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Tonometría Ocular/métodos , Persona de Mediana Edad , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/diagnóstico , Resultado del Tratamiento
18.
Vestn Oftalmol ; 140(2. Vyp. 2): 28-33, 2024.
Artículo en Ruso | MEDLINE | ID: mdl-38739128

RESUMEN

Intravitreal injection (IVI) of anti-angiogenic drugs is one of the most common therapeutic procedures in ophthalmology. In recent years, a new non-contact study method has been developed - anterior segment optical coherence tomography (AS-OCT), which allows the formation of three-dimensional images of the lens and provides more detailed information about its structure and morphology. PURPOSE: This study uses optical coherence tomography method to analyze the risks of developing changes in the posterior lens capsule in patients after IVI of an anti-angiogenic drug. MATERIAL AND METHODS: The study involved 100 people (14 men and 86 women) with a natural lens and neovascular age-related macular degeneration (nAMD). The average age was 70.57±7.98 years. During the study (12 months), all patients underwent IVI of an anti-angiogenic drug aflibercept in the treat-and-extend (T&E) mode. All subjects were divided into 2 groups: with a total number of IVI less than 10 - group 1 (50 patients), and more than 10 IVI - group 2 (50 patients, of which 49 were included in the study). All patients underwent OCT using the Optopol REVO NX device (Poland) with the Anterior B-scan Wide protocol before inclusion in the study, as well as after 3, 6 and 12 months. RESULTS: It was found that the risk of developing a posterior lens capsule rupture, visualized using OCT, depends on the total number of IVI (correlation coefficient 0.473 p=0.001): the more IVI, the higher the probability that damage to the posterior capsule will occur after the next IVI, and after the 15th injection the risk of developing damage to the posterior capsule increases sharply. CONCLUSION: The astudy analyzed the risk factors for the development of posterior lens capsule damage that can be detected using OCT, and presented three risk groups for the development of rupture (or damage) of the posterior lens capsule depending on the number of intravitreal injections performed.


Asunto(s)
Inhibidores de la Angiogénesis , Inyecciones Intravítreas , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Femenino , Masculino , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Anciano , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Cápsula Posterior del Cristalino/diagnóstico por imagen , Cápsula Posterior del Cristalino/efectos de los fármacos , Persona de Mediana Edad , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/diagnóstico
19.
Vestn Oftalmol ; 140(2. Vyp. 2): 73-79, 2024.
Artículo en Ruso | MEDLINE | ID: mdl-38739134

RESUMEN

The management protocol for patients with neovascular age-related macular degeneration (nAMD) involves multiple intravitreal injections (IVI) of anti-VEGF drugs. The ability to reduce the peak intraocular pressure (IOP) rise is greatly important in clinical practice. PURPOSE: This study evaluates the effect of topical hypotensive drugs on the short-term IOP rise after IVI of anti-VEGF drugs in patients with nAMD. MATERIAL AND METHODS: The prospective study included 80 patients with newly diagnosed nAMD. Before the start of treatment, the patients were divided into 4 groups of 20 people each: 1st - controls, who received no prophylactic drugs, in the 2nd, 3rd and 4th groups local instillations of one drop of hypotensive drugs brinzolamide 1%, brinzolamide-timolol, brimonidine-timolol were performed in the conjunctival sac twice: 1 day before the injection (at 20:00) and on the day of the injection 2 hours before the manipulation (at 08:00), respectively. IOP was measured in each patient using ICare Pro non-contact tonometer before injection, as well as 1 min, 30 and 60 min after injection. RESULTS: Prophylactic use of hypotensive drugs was associated with a significant decrease in IOP immediately after IVI compared to the same parameter in the 1st group (p<0.001), the maximum decrease in IOP values was observed when using a fixed combination of brimonidine-timolol by 12.1 mm Hg compared to the controls (p<0.001), the combination of brinzolamide-timolol reduced IOP by 8.5 mm Hg (p<0.001), brinzolamide 1% led to the smallest decrease in IOP - by 5.1 mm Hg (p<0.001). CONCLUSION: Study patients that received instillations of brimonidine-timolol combination of one drop into the conjunctival sac 1 day before the injection and on the day of the injection showed the maximum decrease in IOP compared to patients of the other groups.


Asunto(s)
Inhibidores de la Angiogénesis , Presión Intraocular , Inyecciones Intravítreas , Hipertensión Ocular , Sulfonamidas , Humanos , Masculino , Femenino , Anciano , Presión Intraocular/efectos de los fármacos , Hipertensión Ocular/prevención & control , Hipertensión Ocular/tratamiento farmacológico , Hipertensión Ocular/fisiopatología , Inhibidores de la Angiogénesis/administración & dosificación , Estudios Prospectivos , Sulfonamidas/administración & dosificación , Resultado del Tratamiento , Antihipertensivos/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Tonometría Ocular/métodos , Persona de Mediana Edad , Timolol/administración & dosificación , Tartrato de Brimonidina/administración & dosificación , Soluciones Oftálmicas/administración & dosificación , Tiazinas/administración & dosificación , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/diagnóstico
20.
Vestn Oftalmol ; 140(2. Vyp. 2): 172-179, 2024.
Artículo en Ruso | MEDLINE | ID: mdl-38739148

RESUMEN

Multifocal electroretinography is a valuable diagnostic method for the objective localization and quantitative assessment of functional disorders of the central retina in age-related macular degeneration. It is used to detect early changes, monitor the course of the disease and treatment outcomes. In many cases, multifocal electroretinography is a more sensitive method for detecting functional disorders at the early/intermediate stage of age-related macular degeneration compared to morphological (optical coherence tomography) and subjective (visual acuity, perimetry) testing methods.


Asunto(s)
Electrorretinografía , Degeneración Macular , Retina , Humanos , Electrorretinografía/métodos , Degeneración Macular/diagnóstico , Degeneración Macular/fisiopatología , Retina/diagnóstico por imagen , Retina/fisiopatología , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Diagnóstico Precoz , Progresión de la Enfermedad
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