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1.
Invest Ophthalmol Vis Sci ; 62(12): 9, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34505864

RESUMO

Purpose: In glaucoma, visual field defects in the left and right eye may be non-overlapping, resulting in an intact binocular visual field. In clinical management, these patients are often considered to have normal vision. However, visual performance also relies on binocular processing. The aim of this study was to evaluate binocular visual functions in glaucoma patients with intact binocular visual field, normal visual acuity, and stereoscopy. Methods: We measured in 10 glaucoma patients and 12 age-similar controls: (1) monocular and binocular contrast sensitivity functions (CSF) using a modified quick CSF test to assess binocular contrast summation, (2) dominance during rivalry, and (3) contrast ratio at balance point with a binocular phase combination test. A mirror stereoscope was used to combine the left and right eye image (each 10° horizontally by 12° vertically) on a display. Results: Area under the monocular and binocular CSF was lower in glaucoma compared to healthy (P < 0.001), but the binocular contrast summation ratio did not differ (P = 0.30). For rivalry, the percentage of time of mixed percept was 9% versus 18% (P = 0.056), the absolute difference of the percentage of time of dominance between the two eyes 19% versus 10% (P = 0.075), and the rivalry rate 8.2 versus 12.1 switches per minute (P = 0.017) for glaucoma and healthy, respectively. Median contrast ratio at balance point was 0.66 in glaucoma and 1.03 in controls (P = 0.011). Conclusions: Binocular visual information processing deficits can be found in glaucoma patients with intact binocular visual field, normal visual acuity, and stereoscopy.


Assuntos
Sensibilidades de Contraste/fisiologia , Glaucoma/fisiopatologia , Visão Binocular/fisiologia , Acuidade Visual , Campos Visuais/fisiologia , Percepção Visual/fisiologia , Feminino , Humanos , Masculino , Visão Monocular/fisiologia , Testes de Campo Visual/métodos , Adulto Jovem
2.
Nat Commun ; 12(1): 4877, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385434

RESUMO

Chronically elevated intraocular pressure (IOP) is the major risk factor of primary open-angle glaucoma, a leading cause of blindness. Dysfunction of the trabecular meshwork (TM), which controls the outflow of aqueous humor (AqH) from the anterior chamber, is the major cause of elevated IOP. Here, we demonstrate that mice deficient in the Krüppel-like zinc finger transcriptional factor GLI-similar-1 (GLIS1) develop chronically elevated IOP. Magnetic resonance imaging and histopathological analysis reveal that deficiency in GLIS1 expression induces progressive degeneration of the TM, leading to inefficient AqH drainage from the anterior chamber and elevated IOP. Transcriptome and cistrome analyses identified several glaucoma- and extracellular matrix-associated genes as direct transcriptional targets of GLIS1. We also identified a significant association between GLIS1 variant rs941125 and glaucoma in humans (P = 4.73 × 10-6), further supporting a role for GLIS1 into glaucoma etiology. Our study identifies GLIS1 as a critical regulator of TM function and maintenance, AqH dynamics, and IOP.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Glaucoma/fisiopatologia , Pressão Intraocular/fisiologia , Malha Trabecular/fisiopatologia , Fatores de Transcrição/metabolismo , Animais , Humor Aquoso/metabolismo , Sequenciamento de Cromatina por Imunoprecipitação/métodos , Proteínas de Ligação a DNA/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Glaucoma/genética , Glaucoma/metabolismo , Células HEK293 , Humanos , Pressão Intraocular/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA-Seq/métodos , Malha Trabecular/metabolismo , Fatores de Transcrição/genética
3.
Medicine (Baltimore) ; 100(32): e26938, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397944

RESUMO

BACKGROUND: Glaucoma, is the most common cause of irreversible visual deficits, presents as an injury to the optic nerve and it is mainly associated with elevated intraocular pressure. The main symptom of glaucoma is a reduction of the visual field, which is usually a source of complaint at the advanced stage of disease. Because of visual deficit, gait dysfunctions, including low gait speed and increased bumping into objects, postural sway, and falling are occurred. Many studies have used stopwatch or motion-sensing devices to report on gait function following glaucoma. However, there are few reports on gait dysfunction assessed by examining foot pressure. This study investigated gait ability following glaucoma according to different gait conditions by assessing foot pressure. METHODS: Thirty older adults (15 in the sex- and age-matched normal group and 15 in the glaucoma group) were recruited for this study. All participants were walked under 2 different gait conditions in an F-scan system and the subject' assessments were randomly assigned to rule out the order effect. Conditions included: gait over an obstacle in a straight 6 m path, gait in a straight path without an obstacle in the 6 m path. Gait variables included cadence, gait cycle, stance time, center of force (COF) deviation, and COF excursion. About 10 minutes were taken for gait evaluation. RESULTS: When walking without an obstacle on a 6 m path, there were significant differences between the 2 groups in gait speed, cadence, gait cycle, and stance time (P < .05). There were significant differences when walking with an obstacle on a 6 m path (P < .05). Two-way analysis of variance showed significant effects associated with "glaucoma" not gait condition on all outcomes except for COF deviation and excursion. Also, there was no the interaction effect between "glaucoma" and "gait condition." CONCLUSION: We demonstrated that glaucoma patients selected the gait strategy such as lower gait function in both gait conditions particularly, slower gait speed and cadence and longer gait cycle and stance time, as determined by examining foot pressure. We believe that our results could help to improve the quality of life of patients with glaucoma.


Assuntos
Pé/fisiopatologia , Marcha/fisiologia , Glaucoma/fisiopatologia , Qualidade de Vida , Sapatos , Caminhada/fisiologia , Idoso , Fenômenos Biomecânicos , Estudos Transversais , Feminino , Humanos , Masculino , Equilíbrio Postural/fisiologia , Pressão , Velocidade de Caminhada/fisiologia
4.
Exp Eye Res ; 210: 108717, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34348130

RESUMO

The adult mammal lacks the ability to regenerate neurons lost to retinal damage or disease in a meaningful capacity. However, previous studies from this laboratory have demonstrated that PNU-282987, an α7 nicotinic acetylcholine receptor agonist, elicits a robust neurogenic response in the adult murine retina. With eye drop application of PNU-282987, Müller glia cells re-enter the cell cycle and produce progenitor-like cells that can differentiate into various types of retinal neurons. In this study, we analyzed the regenerative capability of PNU-282987 in two retinal disease models and identified the source of newly regenerated neurons. Wild-type mice and mice with a transgenic Müller-glia lineage tracer were manipulated to mimic loss of retinal cells associated with glaucoma or photoreceptor degeneration. Following treatment with PNU-282987, the regenerative response of retinal neurons was quantified and characterized. After onset of photoreceptor degeneration, PNU-282987 was able to successfully regenerate both rod and cone photoreceptors. Quantification of this response demonstrated significant regeneration, restoring photoreceptors to near wild-type density. In mice that had glaucoma-like conditions induced, PNU-282987 treatment led to a significant increase in retinal ganglion cells. Retrograde labeling of optic nerve axon fibers demonstrated that newly regenerated axons projected into the optic nerve. Lineage tracing analysis demonstrated that these new neurons were derived from Müller glia. These results demonstrate that PNU-282987 can induce retinal regeneration in adult mice following onset of retinal damage. The ability of PNU-282987 to regenerate retinal neurons in a robust manner offers a new direction for developing novel and potentially transformative treatments to combat neurodegenerative disease.


Assuntos
Benzamidas/farmacologia , Compostos Bicíclicos com Pontes/farmacologia , Modelos Animais de Doenças , Regeneração Nervosa/fisiologia , Degeneração Retiniana/tratamento farmacológico , Células Ganglionares da Retina/fisiologia , Neurônios Retinianos/fisiologia , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Animais , Ciclo Celular , Células Ependimogliais/efeitos dos fármacos , Células Ependimogliais/metabolismo , Glaucoma/fisiopatologia , Pressão Intraocular/fisiologia , Camundongos , Camundongos Endogâmicos , Camundongos Transgênicos , Neurogênese , Agonistas Nicotínicos/farmacologia , Degeneração Retiniana/metabolismo
5.
Exp Eye Res ; 210: 108728, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34390734

RESUMO

PURPOSE: Activation of bone morphogenetic protein (BMP) 4 signaling promotes the survival of retinal ganglion cell (RGC) after acute injury. Chordin-like 1 (CHRDL1) is an endogenous BMP antagonist. In this study, we researched whether CHRDL1 was involved in BMP4 signaling and regulation of RGC degeneration in a mouse model of glaucoma. METHODS: Magnetic microbeads were intracameral injected to induce experimental glaucoma in a mouse model. A recombinant adeno-associated virus (rAAV) system was designed for overexpression of BMP4 or CHRDL1 in mouse retina. Immunohistochemistry and hematoxylin-eosin (HE) stains were performed to identify changes in retinal morphology. Electroretinogram (ERG) recordings were used to assess changes in visual function. RESULTS: The mRNA expression levels of Bmp4 and its downstream BMPRIa, small mothers against decapentaplegic 1 (Smad1), were significantly upregulated in retinas with glaucoma. RGC survival was significantly enhanced in the beads + AAV-BMP4 group and significantly reduced in the beads + AAV-CHRDL1 group, compared with the beads + AAV-EGFP group. Similar results were observed in retinal explant culture in vitro. Consistent with these findings, the photopic negative response (PhNR)responses in ERG, which indicate RGC function, were restored in mice overexpressing BMP4, whereas a-wave and b-wave responses were not. Activation of CHRLD1 inhibited Smad1/5/8 phosphorylation and exacerbated RGC damage. The expression of Glial fibrillary acidic protein (GFAP) was decreased significantly in beads + AAV-BMP4 group. CONCLUSIONS: BMP4 promoted RGC survival and visual function in an experimental glaucoma model. Activation of CHRDL1 exaggerated RGC degeneration by inhibiting the BMP4/Smad1/5/8 pathway. The mechanism of BMP4/Smad1/5/8 pathway may be related to the inhibition of glial cell activation. Our studies suggested that BMP4 and CHRLD1 might serve as therapeutic targets in glaucoma.


Assuntos
Proteína Morfogenética Óssea 4/genética , Modelos Animais de Doenças , Proteínas do Olho/metabolismo , Regulação da Expressão Gênica/fisiologia , Glaucoma/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Células Ganglionares da Retina/fisiologia , Animais , Proteína Morfogenética Óssea 4/antagonistas & inibidores , Sobrevivência Celular , Dependovirus/genética , Eletrorretinografia , Vetores Genéticos , Glaucoma/fisiopatologia , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Pressão Intraocular/fisiologia , Injeções Intravítreas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Retina/fisiopatologia
6.
Invest Ophthalmol Vis Sci ; 62(9): 9, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34232257

RESUMO

Purpose: Glaucoma is a multifactorial disease, causing retinal ganglion cells (RGCs) and optic nerve degeneration. The role of diabetes as a risk factor for glaucoma has been postulated but still not unequivocally demonstrated. The purpose of this study is to clarify the effect of diabetes in the early progression of glaucomatous RGC dysfunction preceding intraocular pressure (IOP) elevation, using the DBA/2J mouse (D2) model of glaucoma. Methods: D2 mice were injected with streptozotocin (STZ) obtaining a combined model of diabetes and glaucoma (D2 + STZ). D2 and D2 + STZ mice were monitored for weight, glycemia, and IOP from 3.5 to 6 months of age. In addition, the activity of RGC and outer retina were assessed using pattern electroretinogram (PERG) and flash electroretinogram (FERG), respectively. At the end point, RGC density and astrogliosis were evaluated in flat mounted retinas. In addition, Müller cell reactivity was evaluated in retinal cross-sections. Finally, the expression of inflammation and oxidative stress markers were analyzed. Results: IOP was not influenced by time or diabetes. In contrast, RGC activity resulted progressively decreased in the D2 group independently from IOP elevation and outer retinal dysfunction. Diabetes exacerbated RGC dysfunction, which resulted independent from variation in IOP and outer retinal activity. Diabetic retinas displayed decreased RGC density and increased glial reactivity given by an increment in oxidative stress and inflammation. Conclusions: Diabetes can act as an IOP-independent risk factor for the early progression of glaucoma promoting oxidative stress and inflammation-mediated RGC dysfunction, glial reactivity, and cellular death.


Assuntos
Diabetes Mellitus Experimental/complicações , Glaucoma/fisiopatologia , Pressão Intraocular/fisiologia , Retina/fisiopatologia , Células Ganglionares da Retina/patologia , Animais , Axônios/patologia , Diabetes Mellitus Experimental/fisiopatologia , Eletrorretinografia , Glaucoma/diagnóstico , Glaucoma/etiologia , Camundongos , Camundongos Endogâmicos DBA , Retina/diagnóstico por imagem
7.
Invest Ophthalmol Vis Sci ; 62(9): 5, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34232261

RESUMO

Purpose: To characterize in vivo dendritic changes in retinal ganglion cells (RGCs) after acute (optic nerve transection, ONT) and chronic (experimental glaucoma, EG) optic nerve injury. Methods: ONT and EG (microbead model) were carried out in Thy1-YFP mice in which the entire RGC dendritic arbor was imaged with confocal fluorescence scanning laser ophthalmoscopy over two weeks in the ONT group and over two and six months, respectively, in two (groups 1 and 2) EG groups. Sholl analysis was used to quantify dendritic structure with the parameters: area under the curve (AUC), radius of the dendritic field, peak number of intersections (PI), and distance to the PI (PD). Results: Dendritic changes were observed after three days post-ONT with significant decreases in all parameters at two weeks. In group 1 EG mice, mean (SD) intraocular pressure (IOP) was 15.2 (1.1) and 9.8 (0.3) mmHg in the EG and untreated contralateral eyes, respectively, with a significant corresponding decrease in AUC, PI, and PD, but not radius. In group 2 mice, the respective IOP was 13.1 (1.0) and 8.8 (0.1) mmHg, peaking at two months before trending towards baseline. Over the first two months, AUC, PI, and PD decreased significantly, with no further subsequent changes. The rates of change of the parameters after ONT was 5 to 10 times faster than in EG. Conclusions: Rapid dendritic changes occurred after ONT, while changes in EG were slower and associated with level of IOP increase. The earliest alterations were loss of inner neurites without change in dendritic field.


Assuntos
Células Dendríticas/patologia , Traumatismos do Nervo Óptico/diagnóstico , Células Ganglionares da Retina/patologia , Doença Aguda , Animais , Doença Crônica , Modelos Animais de Doenças , Progressão da Doença , Glaucoma/complicações , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Pressão Intraocular/fisiologia , Camundongos , Microscopia Confocal , Traumatismos do Nervo Óptico/etiologia
8.
Invest Ophthalmol Vis Sci ; 62(9): 35, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34297802

RESUMO

Purpose: We examined structural and functional changes in the outer retina of a mouse model of glaucoma. We examined whether these changes are a secondary consequence of damage in the inner retina and whether neuroprotection of the inner retina also prevents outer retinal changes. Methods: We used an established microbead occlusion model of glaucoma whereby intraocular pressure (IOP) was elevated. Specific antibodies were used to label rod and cone bipolar cells (BCs), horizontal cells (HCs), and retinal ganglion cells (RGCs), as well as synaptic components in control and glaucomatous eyes, to assess structural damage and cell loss. ERG recordings were made to assess outer retina function. Results: We found structural and functional damage of BCs, including significant cell loss and dendritic/axonal remodeling of HCs, following IOP elevation. The first significant loss of both BCs occurred at 4 to 5 weeks after microbead injection. However, early changes in the dendritic structure of RGCs were observed at 3 weeks, but significant changes in the rod BC axon terminal structure were not seen until 4 weeks. We found that protection of inner retinal neurons in glaucomatous eyes by pharmacological blockade of gap junctions or genetic ablation of connexin 36 largely prevented outer retinal damage. Conclusions: Together, our results indicate that outer retinal impairments in glaucoma are a secondary sequalae of primary damage in the inner retina. The finding that neuroprotection of the inner retina can also prevent outer retinal damage has important implications with regard to the targets for effective neuroprotective therapy.


Assuntos
Glaucoma/prevenção & controle , Pressão Intraocular/fisiologia , Ácido Meclofenâmico/administração & dosagem , Neuroproteção/fisiologia , Segmento Interno das Células Fotorreceptoras da Retina/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Modelos Animais de Doenças , Eletrorretinografia , Glaucoma/patologia , Glaucoma/fisiopatologia , Imuno-Histoquímica , Injeções , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica , Segmento Interno das Células Fotorreceptoras da Retina/metabolismo , Segmento Interno das Células Fotorreceptoras da Retina/ultraestrutura
9.
Invest Ophthalmol Vis Sci ; 62(9): 37, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34311470

RESUMO

Purpose: The purpose of this study was to investigate how axial length (AL) changes the relationship of intraocular pressure (IOP) with peripapillary vessel density (pVD) in glaucoma versus non-glaucomatous eyes. Methods: A population-based, cross-sectional study of 2127 African Americans aged 40 years and older in Inglewood, California, were imaged with 6 × 6-mm optic disc optical coherence tomography angiography scans. There were 1028 healthy subjects (1539 eyes) and 65 subjects with glaucoma (86 eyes) who met inclusion criteria. A multivariable linear mixed effects regression model investigated the relationship of IOP on pVD after controlling for signal strength, retinal nerve fiber layer thickness, and age. These results were stratified by AL groups. Results: Higher IOP was a significant predictor of lower pVD among subjects with glaucoma (P = 0.009), but not among healthy subjects (P = 0.26). After stratifying by the sample median AL (23.46 mm), higher IOP was associated with lower pVD among subjects with glaucoma with longer AL (≥ 23.46 mm, P = 0.005), but not among those in the shorter AL (< 23.46 mm, P = 0.45). IOP was not significantly associated with pVD among healthy subjects in either AL stratum. Conclusions: Among subjects with glaucoma with longer AL, IOP was significantly associated with pVD. This relationship was not seen among subjects with glaucoma with shorter AL or non-glaucomatous subjects in either AL group. These findings support the hypothesis that disturbed retinal autoregulation may be present in subjects with glaucoma with longer AL. Longitudinal studies are needed to further investigate whether axial elongation increases glaucoma risk by compromising retinal autoregulation.


Assuntos
Afro-Americanos , Comprimento Axial do Olho/diagnóstico por imagem , Glaucoma/fisiopatologia , Pressão Intraocular/fisiologia , Densidade Microvascular/fisiologia , Disco Óptico/diagnóstico por imagem , Vasos Retinianos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , California/epidemiologia , Estudos Transversais , Feminino , Glaucoma/diagnóstico , Glaucoma/etnologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Tomografia de Coerência Óptica/métodos
10.
Int J Mol Sci ; 22(11)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072647

RESUMO

Steroid-induced glaucoma is a severe pathological condition, sustained by a rapidly progressive increase in intraocular pressure (IOP), which is diagnosed in a subset of subjects who adhere to a glucocorticoid (GC)-based therapy. Molecular and clinical studies suggest that either natural or synthetic GCs induce a severe metabolic dysregulation of Trabecular Meshwork Cells (TMCs), an endothelial-derived histotype with phagocytic and secretive functions which lay at the iridocorneal angle in the anterior segment of the eye. Since TMCs physiologically regulate the composition and architecture of trabecular meshwork (TM), which is the main outflow pathway of aqueous humor, a fluid which shapes the eye globe and nourishes the lining cell types, GCs are supposed to trigger a pathological remodeling of the TM, inducing an IOP increase and retina mechanical compression. The metabolic dysregulation of TMCs induced by GCs exposure has never been characterized at the molecular detail. Herein, we report that, upon dexamethasone exposure, a TMCs strain develops a marked inhibition of the autophagosome biogenesis pathway through an enhanced turnover of two members of the Ulk-1 complex, the main platform for autophagy induction, through the Ubiquitin Proteasome System (UPS).


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Autofagia/efeitos dos fármacos , Dexametasona/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Complexos Multiproteicos/metabolismo , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/genética , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Proliferação de Células/efeitos dos fármacos , Dexametasona/efeitos adversos , Suscetibilidade a Doenças , Glaucoma/etiologia , Glaucoma/metabolismo , Glaucoma/fisiopatologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Complexo de Endopeptidases do Proteassoma/metabolismo
11.
Int J Mol Sci ; 22(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946979

RESUMO

Choline is essential for maintaining the structure and function of cells in humans. Choline plays an important role in eye health and disease. It is a precursor of acetylcholine, a neurotransmitter of the parasympathetic nervous system, and it is involved in the production and secretion of tears by the lacrimal glands. It also contributes to the stability of the cells and tears on the ocular surface and is involved in retinal development and differentiation. Choline deficiency is associated with retinal hemorrhage, glaucoma, and dry eye syndrome. Choline supplementation may be effective for treating these diseases.


Assuntos
Colina/fisiologia , Oftalmopatias/metabolismo , Acetilcolina/biossíntese , Acetilcolina/fisiologia , Animais , Deficiência de Colina/complicações , Deficiência de Colina/fisiopatologia , Retinopatia Diabética/fisiopatologia , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/fisiopatologia , Oftalmopatias/etiologia , Oftalmopatias/fisiopatologia , Dor Ocular/fisiopatologia , Glaucoma/fisiopatologia , Glicerilfosforilcolina/uso terapêutico , Humanos , Aparelho Lacrimal/inervação , Aparelho Lacrimal/metabolismo , Cristalino/metabolismo , Nociceptividade/fisiologia , Nervo Óptico/metabolismo , Sistema Nervoso Parassimpático/fisiopatologia , Fosfatidilcolinas/biossíntese , Fosfolipídeos/metabolismo , Receptores Nicotínicos/fisiologia , Retina/crescimento & desenvolvimento , Retina/metabolismo , Vasos Retinianos/metabolismo , Lágrimas/metabolismo
12.
Exp Eye Res ; 208: 108615, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33971222

RESUMO

Animal models of the Boston keratoprosthesis type 1 (KPro) are needed to study glaucoma damage after KPro implantation to control for confounding comorbidities common in human KPro recipients. The purpose of this study was to determine the feasibility of establishing a reproducible mouse model of glaucoma after KPro surgery, specifically that of a miniaturized mouse model of KPro (mKPro). In the present study, a total of 20 corneas of donor C57BL/6 mice (n = 10) were implanted in one eye of each recipient BALB/C mouse (n = 20), assembled as part of the mKPro, either with or without intraoperative lensectomy. Main feasibility outcomes consisted in incidence rates of loss of tone, capsule nicking, and lens extrusion, as well as acquisition of posterior segment optical coherence tomography (OCT) images. With lensectomy (n = 10), loss of ocular tone and retinal detachment occurred in 100% of mice. Without lensectomy (n = 10), capsule nicking and opening, as well as lens extrusion, occurred in 80% of mice. Causes of these complications included the large proportion of intraocular volume occupied by the lens, the shallow anterior chamber, and thus the lack of available intraocular volume to implant the KPro if the lens remains present. Successful mouse KPro surgery may require a great deal of practice to be useful as a reproducible model. Animal KPro models ought to be pursued further by research teams in future studies.


Assuntos
Córnea/cirurgia , Doenças da Córnea/cirurgia , Glaucoma/etiologia , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Complicações Pós-Operatórias , Próteses e Implantes/efeitos adversos , Tomografia de Coerência Óptica/métodos , Animais , Córnea/patologia , Doenças da Córnea/diagnóstico , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Pressão Intraocular/fisiologia , Camundongos , Acuidade Visual
13.
Life Sci ; 278: 119564, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33961857

RESUMO

AIMS: Elevated intraocular pressure is primarily induced by the increased resistance of conventional outflow of aqueous humor. Dysfunction of the juxtacanalicular region of trabecular meshwork (TM) and Schlemm's canal (SC) endothelium, as the main conventional outflow tissue, have been implicated as the major reasons for the increased resistance. Integrins are widespread in these tissues, especially alpha8 integrin (ITGA8). We aim to investigate the properties of cells expressing ITGA8 in the conventional outflow tissue. MAIN METHODS: Fluorescence in situ hybridization (FISH) and immunofluorescence (IF) were performed to detect the mRNA and protein levels of ITGA8 in human conventional outflow tissue. ITGA8-positive cells were isolated from the cultured human TM cells through a magnetic bead-based approach. Flow Cytometry was used to determine the purification efficiency. The expressions of TM and SC biomarkers and dexamethasone-induced myocilin secretion capacity of ITGA8-positive cells was assessed by Real-time PCR, IF and Western blot. A gel contraction assay was performed to evaluate contractility of ITGA8-positive cells after endothelin 1 treatment. KEY FINDINGS: ITGA8 was found with robust expression near the inner wall of SC endothelium. After purification, the proportion of ITGA8-positive cells were increased by about 10%. ITGA8-positive cells were identified with the properties as SC endothelial cells, such as more robust expressions of SC biomarkers, less dexamethasone-inducible myocilin expression, and stronger contractility. SIGNIFICANCE: This study demonstrated that cells expressing ITGA8 in SC region possess more properties as SC endothelial cells. Our data implicate a crucial role of ITGA8 in aqueous humor (AH) outflow resistance regulation.


Assuntos
Humor Aquoso/metabolismo , Células Endoteliais/metabolismo , Glaucoma/metabolismo , Cadeias alfa de Integrinas/metabolismo , Pressão Intraocular , Malha Trabecular/metabolismo , Biomarcadores/metabolismo , Sobrevivência Celular , Proteínas do Citoesqueleto/metabolismo , Dexametasona/farmacologia , Endotelina-1/metabolismo , Endotélio/metabolismo , Proteínas do Olho/metabolismo , Glaucoma/fisiopatologia , Glucocorticoides/metabolismo , Glicoproteínas/metabolismo , Humanos , Hibridização in Situ Fluorescente , Integrinas/metabolismo
14.
Rom J Ophthalmol ; 65(1): 15-19, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33817428

RESUMO

Primary open angle glaucoma (POAG) is a multifactorial optic neuropathy, which progresses in a chronic manner. Several etiological factors are involved, including genetic factors, race, age, IOP or vascular, systemic factors. IOP has an established role in the initiation and evolution of glaucoma, but its interactions with additional risk factors are complex. We propose the notion of the Glaucoma Etiological Area (GEA), as a representation of all the elements acting in collaboration in the physiopathology of each glaucoma case. When combined in different proportions, these elements may trigger the typical glaucomatous optic neuropathy (GON). We know that the statistical values of IOP are valid for normal eyes, but the glaucoma eye is not a normal eye. The notion of GEA can open a new perspective to interpret IOP values and to assess the true value of IOP control as a treatment for glaucoma. Applying the GEA theory allows us to tune the role of IOP. Additional factors, such as ocular properties (RGCL status, CCT, IOP fluctuation curve), ocular comorbidities (PEX, PDS), systemic comorbidities (arterial hypertension, vasospastic diseases such as migraines or Reynaud's syndrome) or patient's attitude towards glaucoma management (treatment compliance, access to follow-up and treatment) may greatly influence the evolution of GON and should be viewed holistically when developing a management plan for each patient. Applying the notion of GEA in clinical practice allows a more realistic approach of the pathophysiology of the disease and for a glaucoma treatment that is tailored to each patient. Abbreviations: AG = advanced glaucoma, BP = blood pressure, CCT = central corneal thickness, CIGTS = Collaborative Initial Glaucoma Treatment Study, CNTGS = Collaborative Normal-Tension Glaucoma Study, EMGT = Early Manifest Glaucoma Trial, GEA = glaucoma etiological area, GON = glaucomatous optic neuropathy, IOP = intraocular pressure, NTG = Normal Tension Glaucoma, OHTS = Ocular Hypertension Study, PDS = Pigmentary dispersion syndrome, PEX = Pseudoexfoliation syndrome, POAG - primary open-angle glaucoma, RGCL = retinal ganglion cell layer, VFL = visual field loss.


Assuntos
Gerenciamento Clínico , Glaucoma/terapia , Pressão Intraocular/fisiologia , Nervo Óptico/patologia , Células Ganglionares da Retina/patologia , Sistema Nervoso Simpático/fisiopatologia , Campos Visuais/fisiologia , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Humanos
15.
Int J Mol Sci ; 22(9)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33925045

RESUMO

Glaucomatous optic neuropathies have been regarded as diseases caused by high intraocular pressure for a long time, despite the concept of vascular glaucoma dating back to von Graefe in 1854. Since then, a tremendous amount of knowledge about the ocular vasculature has been gained; cohort studies have established new vascular risk factors for glaucoma as well as identifying protective measures acting on blood vessels. The knowledge about the physiology and pathophysiology of the choroidal, retinal, as well as ciliary and episcleral circulation has also advanced. Only recently have novel drugs based on that knowledge been approved for clinical use, with more to follow. This review provides an overview of the current vascular concepts in glaucoma, ranging from novel pathogenesis insights to promising therapeutic approaches, covering the supply of the optic nerve head as well as the aqueous humor production and drainage system.


Assuntos
Glaucoma/etiologia , Animais , Circulação Sanguínea/fisiologia , Pressão Sanguínea/fisiologia , Olho/irrigação sanguínea , Glaucoma/tratamento farmacológico , Glaucoma/fisiopatologia , Hemodinâmica/fisiologia , Humanos , Pressão Intraocular/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Fatores de Risco
16.
Invest Ophthalmol Vis Sci ; 62(4): 12, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33844828

RESUMO

Purpose: The purpose of this study was to determine if the rate of change in the depth of the surface of the lamina cribrosa due to glaucomatous remodeling differs between glaucoma patients of African descent (AD) and European descent (ED). Methods: There were 1122 images taken longitudinally over an average of 3 years (range = 0.9-4.1 years) from 122 patients with glaucoma followed in the African Descent and Glaucoma Evaluation Study (ADAGES) and Diagnostic Intervention and Glaucoma Study (DIGS) were automatically segmented to compute anterior lamina cribrosa surface depth (ALCSD). The rate of ALCSD change was compared across racial groups after adjusting for baseline characteristics known to be associated with ALCSD or disease progression (visual field, ALCSD, corneal thickness, optic disk size, and age). Results: After adjusting for all other covariates, the ED group had significantly greater ALCSD posterior migration (deepening) than the AD group (difference = 2.57 µm/year, P = 0.035). There was a wider range of ALCSD change in the ED compared with the AD group, and more individuals had greater magnitude of both deepening and shallowing. No other covariates measured at baseline had independent effects on the longitudinal changes in ALCSD (baseline visual field severity, baseline ALCSD, corneal thickness, Bruch's membrane opening [BMO] area, or age). Conclusions: Glaucomatous remodeling of the lamina cribrosa differs between AD and ED patients with glaucoma. Unlike the cross-sectional associations seen with aging, in which a deeper ALCSD was seen with age in the ED group, glaucomatous remodeling in this longitudinal study resulted in more posterior migration of ALCSD in ED compared to AD patients.


Assuntos
Afro-Americanos , Lâmina Basilar da Corioide/patologia , Glaucoma/etnologia , Pressão Intraocular/fisiologia , Disco Óptico/patologia , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Idoso , Estudos Transversais , Europa (Continente)/etnologia , Feminino , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Humanos , Incidência , Masculino , Fibras Nervosas/patologia , Fatores Raciais , Estados Unidos/epidemiologia , Campos Visuais
17.
Invest Ophthalmol Vis Sci ; 62(4): 20, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33856415

RESUMO

Purpose: Inflammatory cytokines are involved in glaucoma pathogenesis. The purpose is to compare cytokine levels in the tear film of Boston keratoprosthesis (KPro) patients with and without glaucoma, relative to controls, and correlate levels with clinical parameters. Methods: This cross-sectional study enrolled 58 eyes (58 patients): 41 KPro eyes with glaucoma, 7 KPro eyes without glaucoma, and 10 healthy controls. Twenty-seven cytokines were measured by multiplex bead immunoassay. Intraocular pressure (IOP), cup-to-disk ratio (CDR), retinal nerve fiber layer, visual acuity, topical medications, and angle closure were assessed in all KPro eyes. Cytokine levels between groups were analyzed by nonparametric tests, and correlations with clinical parameters by Spearman's test. Results: Levels of TNF-ɑ, IL-1ß, FGF-basic, and IFN-É£ were significantly higher in KPro with glaucoma compared to KPro without (P = 0.020; 0.008; 0.043; 0.018, respectively). KPro groups had similar characteristics and topical antibiotic/steroid regimen. Levels of IL-1Ra, IL-15, VEGF, and RANTES were significantly higher in KPro with glaucoma compared to controls (P < 0.001; = 0.034; < 0.001; = 0.001, respectively). IL-1ß and IFN-É£ levels were positively correlated with CDR (r = 0.309, P = 0.039 and r = 0.452, P = 0.006, respectively) and IOP (r = 0.292, P = 0.047 and r = 0.368, P = 0.023, respectively). TNF-α and FGF-basic levels were positively correlated with CDR (r = 0.348, P = 0.022 and r = 0.344, P = 0.021, respectively). Conclusions: TNF-α, IL-1ß, FGF-basic, IFN-É£ are elevated in tears of KPro patients with glaucoma and correlate with CDR and IOP. These results show, for the first time in humans, concordance with documented elevations of TNF-α and IL-1ß in the murine KPro model. Ocular surface inflammation may reflect inflammatory processes of KPro glaucoma.


Assuntos
Órgãos Artificiais , Doenças da Córnea/cirurgia , Citocinas/metabolismo , Glaucoma/complicações , Pressão Intraocular , Lágrimas/metabolismo , Acuidade Visual , Idoso , Biomarcadores/metabolismo , Doenças da Córnea/complicações , Doenças da Córnea/metabolismo , Estudos Transversais , Feminino , Seguimentos , Glaucoma/metabolismo , Glaucoma/fisiopatologia , Humanos , Masculino , Estudos Prospectivos
18.
Med Clin North Am ; 105(3): 493-510, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33926643

RESUMO

Glaucoma is the leading cause of irreversible blindness worldwide. The global prevalence of glaucoma in people aged 40 to 80 years is estimated to be 3.5%. With the growing number and proportion of older persons in the population, it is projected that 111.8 million people will have glaucoma in 2040. Currently available treatments cannot reverse glaucomatous damage to the visual system; however, early diagnosis and treatment can prevent progression of the disease. In most cases, glaucoma is a chronic condition that requires lifelong management. This article reviews the pathophysiology, classification, clinical manifestations, diagnosis, and management of glaucoma.


Assuntos
Glaucoma , Glaucoma/classificação , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Glaucoma/terapia , Humanos , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia
19.
Semin Ophthalmol ; 36(4): 310-314, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-33689562

RESUMO

Technological advances provide a number of options for glaucoma monitoring outside the office setting, including home-based tonometry and perimetry. This has the potential to revolutionize management of this chronic disease, improve access to care, and enhance patient engagement. Here, we provide an overview of existing technologies for home-based glaucoma monitoring. We also discuss areas for future research and the potential applications of these technologies to telemedicine, which has been brought to the forefront during the ongoing COVID-19 pandemic.


Assuntos
Técnicas de Diagnóstico Oftalmológico/tendências , Glaucoma/diagnóstico , Monitorização Ambulatorial , Telemedicina/tendências , Telemetria/instrumentação , Tecnologia Biomédica/tendências , Glaucoma/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Oftalmologia/tendências , Autocuidado/métodos , Tomografia de Coerência Óptica/métodos , Tonometria Ocular/métodos , Testes de Campo Visual/métodos
20.
PLoS One ; 16(3): e0248851, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33755663

RESUMO

PURPOSE: To evaluate association between ocular blood flow biomarkers and lamina cribrosa parameters in normotensive glaucoma suspects compared to glaucoma patients and healthy controls. METHODS: A total of 211 subjects (72 normotensive glaucoma suspects, 70 with primary open-angle glaucoma and 69 controls) were included. Ocular blood flow biomarkers in ophthalmic artery, central retinal artery, as well as in nasal and temporal short posterior ciliary arteries were measured using colour Doppler imaging. Lamina cribrosa position was assessed by measuring its depth, deflection depth, lamina cribrosa shape index and its horizontal equivalent (LCSIH) on B-scan images obtained using optical coherence tomography. RESULTS: Ocular blood flow biomarkers in glaucoma patients were statistically significantly reduced when compared to healthy controls in peak systolic velocity (PSV) (P = 0.001 in ophthalmic artery and P<0.001 in central retinal artery) and mean flow velocity (Vm) (P = 0.008 in ophthalmic artery and P = 0.008 in central retinal artery), but not statistically significantly different to that of glaucoma suspects except for PSV in central retinal artery (P = 0.011). Statistically significant correlations corrected for age, central corneal thickness and intraocular pressure were found in glaucoma patients between LCSIH and end diastolic velocity of central retinal artery (P = 0.011), and of nasal short posterior ciliary artery (P = 0.028), and between LCSIH and Vm of central retinal artery (P = 0.011) and of nasal short posterior ciliary artery (P = 0.007). No significant correlations were observed between these parameters in glaucoma suspects and healthy controls. CONCLUSIONS: Impaired ocular blood flow associated with the deformation of lamina cribrosa was found in glaucoma patients, whereas glaucoma suspects had similar lamina cribrosa shape to glaucoma patients but that deformation was not associated with ocular blood flow biomarkers.


Assuntos
Biomarcadores/metabolismo , Olho/irrigação sanguínea , Glaucoma/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Olho/fisiopatologia , Feminino , Glaucoma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/fisiopatologia , Fluxo Sanguíneo Regional , Artéria Retiniana/diagnóstico por imagem , Artéria Retiniana/patologia , Artéria Retiniana/fisiopatologia , Ultrassonografia Doppler em Cores
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