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Glaucoma is a blinding disease. Reduction of intraocular pressure (IOP) is the mainstay of treatment, but current drugs show side effects or become progressively ineffective, highlighting the need for novel compounds. We have synthesized a family of perhydro-1,4-oxazepine derivatives of digoxin, the selective inhibitor of Na,K-ATPase. The cyclobutyl derivative (DcB) displays strong selectivity for the human α2 isoform and potently reduces IOP in rabbits. These observations appeared consistent with a hypothesis that in ciliary epithelium DcB inhibits the α2 isoform of Na,K-ATPase, which is expressed strongly in nonpigmented cells, reducing aqueous humor (AH) inflow. This paper extends assessment of efficacy and mechanism of action of DcB using an ocular hypertensive nonhuman primate model (OHT-NHP) (Macaca fascicularis). In OHT-NHP, DcB potently lowers IOP, in both acute (24 h) and extended (7-10 days) settings, accompanied by increased aqueous humor flow rate (AFR). By contrast, ocular normotensive animals (ONT-NHP) are poorly responsive to DcB, if at all. The mechanism of action of DcB has been analyzed using isolated porcine ciliary epithelium and perfused enucleated eyes to study AH inflow and AH outflow facility, respectively. 1) DcB significantly stimulates AH inflow although prior addition of 8-Br-cAMP, which raises AH inflow, precludes additional effects of DcB. 2) DcB significantly increases AH outflow facility via the trabecular meshwork (TM). Taken together, the data indicate that the original hypothesis on the mechanism of action must be revised. In the OHT-NHP, and presumably other species, DcB lowers IOP by increasing AH outflow facility rather than by decreasing AH inflow.NEW & NOTEWORTHY When applied topically, a cyclobutyl derivative of digoxin (DcB) potently reduces intraocular pressure in an ocular hypertensive nonhuman primate model (Macaca fascicularis), associated with increased aqueous humor (AH) flow rate (AFR). The mechanism of action of DcB involves increased AH outflow facility as detected in enucleated perfused porcine eyes and, in parallel, increased (AH) inflow as detected in isolated porcine ciliary epithelium. DcB might have potential as a drug for the treatment of open-angle human glaucoma.
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Humor Aquoso , Digoxina , Pressão Intraocular , Macaca fascicularis , Hipertensão Ocular , Animais , Pressão Intraocular/efeitos dos fármacos , Digoxina/farmacologia , Humor Aquoso/metabolismo , Humor Aquoso/efeitos dos fármacos , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/fisiopatologia , Hipertensão Ocular/metabolismo , Modelos Animais de Doenças , Glaucoma/tratamento farmacológico , Glaucoma/metabolismo , Glaucoma/fisiopatologia , Coelhos , Humanos , Corpo Ciliar/efeitos dos fármacos , Corpo Ciliar/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Masculino , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/metabolismoRESUMO
To explore the temporal profile of retinal proteomes specific to primary and secondary retinal ganglion cell (RGC) loss. Unilateral partial optic nerve transection (pONT) was performed on the temporal side of the rat optic nerve. Temporal and nasal retinal samples were collected at 1, 4 and 8 weeks after pONT (n = 4 each) for non-biased profiling with a high-resolution hybrid quadrupole time-of-flight mass spectrometry running on label-free SWATHTM acquisition (SCIEX). An information-dependent acquisition ion library was generated using ProteinPilot 5.0 and OneOmics cloud bioinformatics. Combined proteome analysis detected 2531 proteins with a false discovery rate of <1%. Compared to the nasal retina, 10, 25 and 61 significantly regulated proteins were found in the temporal retina at 1, 4, and 8 weeks, respectively (p < 0.05, FC ≥ 1.4 or ≤0.7). Eight proteins (ALDH1A1, TRY10, GFAP, HBB-B1, ALB, CDC42, SNCG, NEFL) were differentially expressed for at least two time points. The expressions of ALDH1A1 and SNCG at nerve fibers were decreased along with axonal loss. Increased ALDH1A1 localization in the inner nuclear layer suggested stress response. Increased GFAP expression demonstrated regional reactivity of astrocytes and Muller cells. Meta-analysis of gene ontology showed a pronounced difference in endopeptidase and peptidase inhibitor activity. Temporal proteomic profiling demonstrates established and novel protein targets associated with RGC damage.
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Secretion of melatonin, a natural hormone whose receptors are present in the ciliary epithelium, displays diurnal variation in the aqueous humor (AH), potentially contributing to the regulation of intraocular pressure. This study aimed to determine the effects of melatonin on AH secretion in porcine ciliary epithelium. The addition of 100 µM melatonin to both sides of the epithelium significantly increased the short-circuit current (Isc) by ~40%. Stromal administration alone had no effect on the Isc, but aqueous application triggered a 40% increase in Isc, similar to that of bilateral application without additive effect. Pre-treatment with niflumic acid abolished melatonin-induced Isc stimulation. More importantly, melatonin stimulated the fluid secretion across the intact ciliary epithelium by ~80% and elicited a sustained increase (~50-60%) in gap junctional permeability between pigmented ciliary epithelial (PE) cells and non-pigmented ciliary epithelial (NPE) cells. The expression of MT3 receptor was found to be >10-fold higher than that of MT1 and MT2 in porcine ciliary epithelium. Aqueous pre-treatment with MT1/MT2 antagonist luzindole failed to inhibit the melatonin-induced Isc response, while MT3 antagonist prazosin pre-treatment abolished the Isc stimulation. We conclude that melatonin facilitates Cl- and fluid movement from PE to NPE cells, thereby stimulating AH secretion via NPE-cell MT3 receptors.
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Melatonina , Suínos , Melatonina/farmacologia , Melatonina/metabolismo , Humor Aquoso/metabolismo , Epitélio Pigmentado Ocular/metabolismo , Epitélio/metabolismo , Células Epiteliais/metabolismo , Proteínas de Transporte/metabolismo , Corpo Ciliar/metabolismo , AnimaisRESUMO
Elevated intraocular pressure (IOP) is a major risk factor for glaucoma that results from impeded fluid drainage. The increase in outflow resistance is caused by trabecular meshwork (TM) cell dysfunction and excessive extracellular matrix (ECM) deposition. Baicalein (Ba) is a natural flavonoid and has been shown to regulate cell contraction, fluid secretion, and ECM remodeling in various cell types, suggesting the potential significance of regulating outflow resistance and IOP. We demonstrated that Ba significantly lowered the IOP by about 5 mmHg in living mice. Consistent with that, Ba increased the outflow facility by up to 90% in enucleated mouse eyes. The effects of Ba on cell volume regulation and contractility were examined in primary human TM (hTM) cells. We found that Ba (1-100 µM) had no effect on cell volume under iso-osmotic conditions but inhibited the regulatory volume decrease (RVD) by up to 70% under hypotonic challenge. In addition, Ba relaxed hTM cells via reduced myosin light chain (MLC) phosphorylation. Using iTRAQ-based quantitative proteomics, 47 proteins were significantly regulated in hTM cells after a 3-h Ba treatment. Ba significantly increased the expression of cathepsin B by 1.51-fold and downregulated the expression of D-dopachrome decarboxylase and pre-B-cell leukemia transcription factor-interacting protein 1 with a fold-change of 0.58 and 0.40, respectively. We suggest that a Ba-mediated increase in outflow facility is triggered by cell relaxation via MLC phosphorylation along with inhibiting RVD in hTM cells. The Ba-mediated changes in protein expression support the notion of altered ECM homeostasis, potentially contributing to a reduction of outflow resistance and thereby IOP.
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Oftalmopatias , Flavanonas , Animais , Humor Aquoso/metabolismo , Oftalmopatias/metabolismo , Flavanonas/metabolismo , Flavanonas/farmacologia , Pressão Intraocular , Camundongos , Cadeias Leves de Miosina/metabolismo , Malha Trabecular/metabolismoRESUMO
Rho-kinase (ROCK) inhibitors, a novel class of anti-glaucoma agents, act by increasing the aqueous humor outflow through the conventional trabecular meshwork pathway. However, the downstream signaling consequences of the ROCK inhibitor are not completely understood. Our data show that Y39983, a selective ROCK inhibitor, could induce filamentous actin remodeling, reduced cell motility (as measured by cell migration), and transepithelial resistance in primary human TM (hTM) cells. After 2 days Y39983 treatment of hTM cells, a proteomic study identified 20 proteins whose expression was significantly altered. Pathway analysis of those proteins revealed the involvement of the p53 pathway, integrin signaling pathway, and cytoskeletal pathway regulation by Rho GTPase. Thrombospondin-1 (TSP1), a matricellular protein that is increased in glaucoma patients, was downregulated fivefold following Y39983 treatment. More importantly, both TSP1 antagonist leucine-serine-lysine-leucine (LSKL) and small interfering RNA (siRNA) reduced TSP1 gene and protein expressions as well as hTM cell migration. In the presence of Y39983, no further inhibition of cell migration resulted after LSKL and TSP1 siRNA knockdown. Likewise, LSKL triggered a dose-dependent increase in outflow facility in ex vivo mouse eyes, to a similar extent as Y39983 (83.8% increase by Y39983 vs. 71.2% increase by LSKL at 50 µM). There were no additive effects with simultaneous treatment with LSKL and Y39983, supporting the notion that the effects of ROCK inhibition were mediated by TSP1.
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Agentes Antiglaucoma/farmacologia , Inibidores Enzimáticos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Trombospondinas/metabolismo , Quinases Associadas a rho/metabolismo , Animais , Humor Aquoso/metabolismo , Citoesqueleto/metabolismo , Pressão Intraocular/efeitos dos fármacos , Camundongos , Fosforilação , Proteômica , Transdução de Sinais/efeitos dos fármacos , Malha Trabecular/efeitos dos fármacos , Proteínas rho de Ligação ao GTP/efeitos dos fármacos , Proteínas rho de Ligação ao GTP/metabolismoRESUMO
Our previous research showed that increased phosphorylation of connexin (Cx)36 indicated extended coupling of AII amacrine cells (ACs) in the rod-dominant mouse myopic retina. This research will determine whether phosphorylation at serine 276 of Cx35-containing gap junctions increased in the myopic chicken, whose retina is cone-dominant. Refractive errors and ocular biometric dimensions of 7-days-old chickens were determined following 12 h and 7 days induction of myopia by a -10D lens. The expression pattern and size of Cx35-positive plaques were examined in the early (12 h) and compensated stages (7 days) of lens-induced myopia (LIM). At the same time, phosphorylation at serine 276 (functional assay) of Cx35 in strata 5 (S5) of the inner plexiform layer was investigated. The axial length of the 7 days LIM eyes was significantly longer than that of non-LIM controls (P < 0.05). Anti-phospho-Ser276 (Ser276-P)-labeled plaques were significantly increased in LIM retinas at both 12 h and 7 days. The density of Ser276-P of Cx35 was observed to increase after 12 h LIM. In the meanwhile, the areas of existing Cx35 plaques did not change. As there was more phosphorylation of connexin35 at Ser276 at both the early and late stages (12 h) and 7 days of LIM chicken retinal activity, the coupling with ACs could be increased in myopia development of the cone-dominated chicken retina.
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Galinhas , Miopia , Animais , Junções Comunicantes , Camundongos , Retina , Células Fotorreceptoras Retinianas ConesRESUMO
PURPOSE: To quantify the defocus characteristics in the near-work environment at home and investigate the relationship with subsequent myopia progression. METHODS: Fifty subjects (aged 7-12 years) were recruited and followed for 1 year. The home near-work environment (writing desk) was measured at a baseline home-visit using the Kinect-for-Windows to capture a 3-dimensional image. The depth values of the image were then converted into scene defocus with respect to the subject's viewpoint. The defocus characteristics were quantified as the dioptric volume (the total amount of net defocus, or DV) and standard deviation of the defocus values (SDD ). Information on home size, time spent outdoors, and in front of a desk were also obtained. Univariate correlation, and multivariate regression were used to assess the association between myopia progression, defocus characteristics, and other co-variates. RESULTS: The baseline spherical equivalent refraction (M) and refraction change over 1 year (∆M) were - 1.51 ± 2.02 D and - 0.56 ± 0.45 D respectively. DV was not significantly correlated with ∆M (Spearman's ρ = -0.25, p = 0.08), while SDD was negatively correlated to ∆M (Spearman's ρ = -0.42, p = 0.003). Although SDD was not a significant predictor in multivariate analysis, the regional DV at 15°-20° eccentricity was significant (p = 0.001). Home size (F2,50 = 7.01, p = 0.002) and time spent outdoors (Independent t = -2.13, p = 0.04) were also associated with ∆M, but not time spent in front of desk (Independent t = 0.78, p = 0.44). CONCLUSION: The defocus profile in the home environment within the para-central field of view is associated with childhood refractive error development.
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Óculos , Miopia Degenerativa/etiologia , Refração Ocular/fisiologia , Criança , Feminino , Humanos , Masculino , Miopia Degenerativa/fisiopatologia , Miopia Degenerativa/terapia , Estudos Retrospectivos , Testes VisuaisRESUMO
The molecular pathophysiology of corticosteroid-induced ocular hypertension (CIH) is not well understood. To determine the biological mechanisms of CIH, this study investigated protein expression profiles of human trabecular meshwork (hTM) cells in response to dexamethasone and prednisolone treatment. Both discovery-based sequential windowed data independent acquisition of the total high-resolution mass spectra (SWATH-MS) and targeted based high resolution multiple reaction monitoring (MRM-HR) confirmation were applied using a hybrid quadrupole-time-of-flight mass spectrometer. A comprehensive list of 1759 proteins (1% FDR) was generated from the hTM. Quantitative proteomics revealed 20 differentially expressed proteins (p-value ≤ 0.05 and fold-change ≥ 1.5 or ≤ 0.67) commonly induced by prednisolone and dexamethasone, both at 300 nM. These included connective tissue growth factor (CTGF) and thrombospondin-1 (THBS1), two proteins previously implicated in ocular hypertension, glaucoma, and the transforming growth factor-ß pathway. Their gene expressions in response to corticosteroids were further confirmed using reverse-transcription polymerase chain reaction. Together with other novel proteins identified in the data sets, additional pathways implicated by these regulated proteins were the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, integrin cell surface interaction, extracellular matrix (ECM) proteoglycans, and ECM-receptor interaction. Our results indicated that an integrated platform of SWATH-MS and MRM-HR allows high throughput identification and confirmation of novel and known corticosteroid-regulated proteins in trabecular meshwork cells, demonstrating the power of this technique in extending the current understanding of the pathogenesis of CIH.
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Hipertensão Ocular/genética , Proteômica , Transdução de Sinais/genética , Malha Trabecular/metabolismo , Adulto , Idoso , Linhagem Celular , Pré-Escolar , Fator de Crescimento do Tecido Conjuntivo/genética , Dexametasona/administração & dosagem , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/genética , Feminino , Perfilação da Expressão Gênica/métodos , Glaucoma/tratamento farmacológico , Glaucoma/genética , Glaucoma/patologia , Humanos , Masculino , Espectrometria de Massas , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/patologia , Prednisolona/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Trombospondina 1/genética , Malha Trabecular/efeitos dos fármacosRESUMO
PURPOSE: People in Hong Kong generally live in a densely populated area and their homes are smaller compared with most other cities worldwide. Interestingly, East Asian cities with high population densities seem to have higher myopia prevalence, but the association between them has not been established. This study investigated whether the crowded habitat in Hong Kong is associated with refractive error among children. METHODS: In total, 1075 subjects [Mean age (S.D.): 9.95 years (0.97), 586 boys] were recruited. Information such as demographics, living environment, parental education and ocular status were collected using parental questionnaires. The ocular axial length and refractive status of all subjects were measured by qualified personnel. RESULTS: Ocular axial length was found to be significantly longer among those living in districts with a higher population density (F2,1072 = 6.15, p = 0.002) and those living in a smaller home (F2,1072 = 3.16, p = 0.04). Axial lengths were the same among different types of housing (F3,1071 = 1.24, p = 0.29). Non-cycloplegic autorefraction suggested a more negative refractive error in those living in districts with a higher population density (F2,1072 = 7.88, p < 0.001) and those living in a smaller home (F2,1072 = 4.25, p = 0.02). After adjustment for other confounding covariates, the population density and home size also significantly predicted axial length and non-cycloplegic refractive error in the multiple linear regression model, while axial length and refractive error had no relationship with types of housing. CONCLUSIONS: Axial length in children and childhood refractive error were associated with high population density and small home size. A constricted living space may be an environmental threat for myopia development in children.
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Comprimento Axial do Olho/fisiologia , Exposição Ambiental/efeitos adversos , Miopia/epidemiologia , Refração Ocular/fisiologia , Criança , Feminino , Seguimentos , Hong Kong/epidemiologia , Humanos , Masculino , Miopia/fisiopatologia , Prevalência , Estudos RetrospectivosRESUMO
BACKGROUND: Elevated levels of nitric oxide (NO(â¢) ), a pro-oxidant that has been associated with numerous retinal diseases, have been implicated in experimental glaucoma models. This study investigated the oxidative effects of sodium nitroprusside (SNP), a nitric oxide donor, on the retinal lipids and proteins and evaluated the potential protective effects of glutathione (GSH). METHODS: Porcine retinal homogenates were incubated with 0, 1, 2, 3, 4 and 5 µm SNP. Malondialdehyde (MDA) levels were assayed spectrophotometrically to quantify lipid peroxidation. Differential protein expressions of 3 µm SNP-treated retinal homogenates were compared with controls after the conduction of two-dimensional gel electrophoresis. Mass spectrometric data was used to identify proteins in NCBInr database. Furthermore, GSH was co-incubated with 3 µm SNP-treated retinal homogenates. MDA levels and protein expressions were compared with SNP-treated controls. RESULTS: SNP significantly increased retinal-MDA levels (p = 0.0002). 2-D gel electrophoresis images displayed a significant change in 13 protein spot expressions (p < 0.05). GSH suppressed SNP-induced MDA elevation (p < 0.0001) and selected protein changes (p < 0.05). SNP down-regulated paraoxonase/arylesterase 2 precursor (PON2), ß-actin and ß-tubulin; however, these effects were prevented by a co-incubation with GSH, as confirmed by Western blots. CONCLUSIONS: Nitric oxide induced lipid and protein changes in retinal tissues. The effects were partially reversed by co-incubation with GSH. Data from this study suggests that nitric oxide-induced retinal oxidative stress induces specific molecular changes. This may enable us to better understand the pathogenesis of glaucoma. Further studies are indicated to explore potential pharmacological applications of GSH in nitric oxide-related retinal diseases.
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Proteínas do Olho/metabolismo , Glutationa/farmacologia , Peroxidação de Lipídeos , Óxido Nítrico/farmacologia , Estresse Oxidativo/fisiologia , Retina/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Malondialdeído/metabolismo , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Retina/metabolismo , SuínosRESUMO
BACKGROUND: There is currently limited information about ethnic differences in myopia prevalence within mainland China, especially in rural or semi-rural areas. We examined the prevalence of refractive errors, visual impairment and spectacle coverage in school children of varying ethnicity in Turpan, Xinjiang province. METHODS: A community eye care service was provided for five schools. Presenting monocular distance and near visual acuity (VA), and ocular alignment were assessed. Retinoscopy and cycloplegic subjective refraction were performed for participants with presenting visual impairment (distance VA worse than 0.3 logMAR; Snellen 6/12 or 20/40) or abnormal binocular vision. Questionnaires administered prior to the eye examinations were used to collect information regarding personal lifestyle and parental myopia. RESULTS: A total of 646 out of 690 (94%) subjects aged four to 19 years (11.9 ± 2.6; mean ± S.D.) completed the eye examination. Three hundred and eighty-two (59%) of participants were of Uyghur ethnicity, followed by Han, 176 (27%) and Hui, 74 (12%). The mean age of Uyghur, Han and Hui students was 12.3 ± 2.7, 11.4 ± 2.6 and 11.4 ± 2.3 years respectively, in which the Uyghur students were significantly older than the Han and Hui students (F(3,631) = 5.58 p < 0.001). In total, 170 (27%) and 85 (13%) subjects failed the screening examination for one eye or both eyes, respectively. The prevalence of presenting visual impairment was not significantly different among the ethnic groups (p = 0.26). After cycloplegic refraction, most subjects' VA (98%) improved to better than 0.3 logMAR (Snellen 6/12 or 20/40). The prevalence of "clinically-significant myopia" (≤-0.50 dioptres) was 27%, 18% and 13% in Han, Hui and Uyghur children, respectively (p < 0.001). In contrast, Uyghur students had the highest prevalence of astigmatism (Uyghur 12%, Han 5%, Hui 4%). The overall spectacle coverage was 36%, while spectacle coverage among ethnic groups were similar (Han, 41%; Uyghur, 32%; Hui, 41%; χ(2) = 2.23, df = 2, p = 0.33). CONCLUSION: The prevalence of clinically significant myopia varied markedly with ethnicity in school children sampled from a semi-rural region of mainland China (Han > Hui > Uyghur). As reported previously, uncorrected/under-corrected refractive error was the main cause of presenting visual impairment.
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Erros de Refração/etnologia , Transtornos da Visão/etnologia , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Óculos/estatística & dados numéricos , Feminino , Humanos , Estilo de Vida , Masculino , Miopia/etnologia , Prevalência , Erros de Refração/terapia , Transtornos da Visão/terapia , Testes Visuais/métodos , Acuidade Visual , Adulto JovemRESUMO
Traditional Chinese Medicine has a long history in ophthalmology in China. Over 250 kinds of Traditional Chinese Medicine have been recorded in ancient books for the management of eye diseases, which may provide an alternative or supplement to current ocular therapies. However, the core holistic philosophy of Traditional Chinese Medicine that makes it attractive can also hinder its understanding from a scientific perspective - in particular, determining true cause and effect. This review focused on how Traditional Chinese Medicine could be applied to two prevalent ocular diseases, glaucoma, and cataract. The literature on preclinical and clinical studies in both English and Chinese on the use of Traditional Chinese Medicine to treat these two diseases was reviewed. The pharmacological effects, safety profile, and drug-herb interaction of selected herbal formulas were also investigated. Finally, key considerations for conducting future Traditional Chinese Medicine studies are discussed.
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Catarata , Glaucoma , Humanos , Medicina Tradicional Chinesa , China , Glaucoma/tratamento farmacológicoRESUMO
Presently, different types of eye diseases, such as glaucoma, myopia, infection, and dry eyes are treated with topical eye drops. However, due to ocular surface barriers, eye drops require multiple administrations, which may cause several risks, thereby necessitating additional strategies. Some of the key characteristics of an ideal ocular drug delivery system are as follows: (a) good penetration into cornea, (b) high drug retention in the ocular tissues, (c) targetability to the desired regions of the eye, and (d) good bioavailability. It is worthy to note that the corneal epithelial tight junctions hinder the permeation of therapeutics through the cornea. Therefore, it is necessary to design nanocarriers that can overcome these barriers and enhance drug penetration into the inner parts of the eye. Moreover, intelligent multifunctional nanocarriers can be designed to include cavities, which may help encapsulate sufficient amount of the drug. In addition, nanocarriers can be modified with the targeting moieties. Different types of nanocarriers have been developed for ocular drug delivery applications, including emulsions, liposomes, micelles, and nanoparticles. However, these formulations may be rapidly cleared from the eye. The therapeutic use of the nanoparticles (NPs) is also hindered by the non-specific adsorption of proteins on NPs, which may limit their interaction with the cellular moieties or other targeted biological factors. Functional drug delivery systems (DDS), which can offer targeted ocular drug delivery while avoiding the non-specific protein adsorption could exhibit great potential. This could be further realized by the on-demand DDS, which can respond to the stimuli in a spatio-temporal fashion. The cell-mediated DDS offer another valuable platform for ophthalmological drug delivery.
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Background: Virtual reality is a relatively new intervention that has the potential to be used in the treatment of eye and vision problems. This article reviews the use of virtual reality-related interventions in amblyopia, strabismus, and myopia research. Methods: Sources covered in the review included 48 peer-reviewed research published between January 2000 and January 2023 from five electronic databases (ACM Digital Library, IEEE Xplore, PubMed, ScienceDirect and Web of Science). To prevent any missing relevant articles, the keywords, and terms used in the search included "VR", "virtual reality", "amblyopia", "strabismus," and "myopia". Quality assessment and data extraction were performed independently by two authors to form a narrative synthesis to summarize findings from the included research. Results: Total number of 48 references were reviewed. There were 31 studies published on amblyopia, 18 on strabismus, and 6 on myopia, with 7 studies overlapping amblyopia and strabismus. In terms of technology, smartphone-based virtual reality headset viewers were utilized more often in amblyopia research, but commercial standalone virtual reality headsets were used more frequently in myopia and strabismus-related research. The software and virtual environment were mostly developed based on vision therapy and dichoptic training paradigms. Conclusion: It has been suggested that virtual reality technology offers a potentially effective tool for amblyopia, strabismus, and myopia studies. Nonetheless, a variety of factors, especially the virtual environment and systems employed in the data presented, must be explored before determining whether virtual reality can be effectively applied in clinical settings. This review is significant as the technology in virtual reality software and application design features have been investigated and considered for future reference.
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Prolonged electronic screen use can cause digital eye strain. It can be difficult to rectify due to increasing smartphone reliance, potentially leading to serious public health problems. To investigate the association between time spent on smartphones and digital eye strain (DES) among Hong Kong Chinese school-aged children. Of a total of 1,508 students (748 males, 49.6%) from 8 to 14 years old (mean age = 10.91 years, SD = 2.01) who provided valid data on DES, the 1,298 (86%) who completed the DES questionnaire at 1-year follow-up were included in the analysis. DES was measured using a 10-item scale, and the sum of the 10 dichotomised scores was used as the DES total score. The most commonly reported symptoms were eye fatigue (n = 804, 53.3%), blurred vision (changing from reading to distance viewing) (n = 586, 38.9%), and irritated or burning eyes (n = 516, 34.2%). The DES total scores at baseline and 1-year follow-up were 2.91 (SD = 2.90) and 3.20 (SD = 3.19), respectively. Linear regression controlling for demographic and socio-economic confounders showed that participants with baseline smartphone usage of 241 + min/d had a significantly higher baseline total DES score than those with baseline smartphone usage of 0-60 min/d (2.44 vs 3.21, P < 0.001), and participants with baseline smartphone usage of 181-240 min/d had a significantly higher 1-year follow-up total DES score than those with baseline smartphone usage of 0-60 min/d (2.80 vs 3.50, P = 0.003).
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Smartphone , Transtornos da Visão , Masculino , Humanos , Adolescente , Criança , Hong Kong , Inquéritos e Questionários , Estudos Prospectivos , Transtornos da Visão/etiologiaRESUMO
Microglia shift toward an inflammatory phenotype during aging that is thought to exacerbate age-related neurodegeneration. The molecular and cellular signals that resolve neuroinflammation post-injury are largely undefined. Here, we exploit systems genetics methods based on the extended BXD murine reference family and identify IGFBPL1 as an upstream cis-regulator of microglia-specific genes to switch off inflammation. IGFBPL1 is expressed by mouse and human microglia, and higher levels of its expression resolve lipopolysaccharide-induced neuroinflammation by resetting the transcriptome signature back to a homeostatic state via IGF1R signaling. Conversely, IGFBPL1 deficiency or selective deletion of IGF1R in microglia shifts these cells to an inflammatory landscape and induces early manifestation of brain tauopathy and retinal neurodegeneration. Therapeutic administration of IGFBPL1 drives pro-homeostatic microglia and prevents glaucomatous neurodegeneration and vision loss in mice. These results identify IGFBPL1 as a master driver of the counter-inflammatory microglial modulator that presents an endogenous resolution of neuroinflammation to prevent neurodegeneration in eye and brain.
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Microglia , Tauopatias , Camundongos , Animais , Humanos , Microglia/metabolismo , Doenças Neuroinflamatórias , Tauopatias/metabolismo , Inflamação/metabolismo , Encéfalo/metabolismo , Homeostase , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Proteínas Supressoras de Tumor/metabolismoRESUMO
Systemic hypertension or hypertension is a very common chronic age-related disease worldwide. It is typically characterised by a sustained elevation of blood pressure, particularly when the systolic blood pressure and/or diastolic blood pressure are of more than 140 mmHg and 90 mmHg, respectively. If hypertension is not well controlled, it may lead to an increased risk of stroke and heart attack. It has been shown that hypertension is linked to various ocular diseases, including cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma. Glaucoma is the leading cause of irreversible blindness worldwide. Primary open angle glaucoma is the most common form of the disease and is usually characterised by an increase in intraocular pressure. This condition, together with normal tension glaucoma, constitutes open angle glaucoma. Systemic hypertension has been identified as a risk factor for open angle glaucoma. It is speculated that blood pressure is involved in the pathogenesis of open angle glaucoma by altering intraocular pressure or ocular blood flow, or both. Recent evidence has shown that both extremely high and low blood pressure are associated with increased risk of open angle glaucoma. Additional pathogenic mechanisms, including increased inflammation likely to be involved in the development and progression of these two diseases, are discussed.
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Glaucoma de Ângulo Aberto , Hipertensão , Hipertensão Ocular , Pressão Sanguínea/fisiologia , Glaucoma de Ângulo Aberto/etiologia , Humanos , Hipertensão/complicações , Pressão Intraocular , Hipertensão Ocular/etiologia , Tonometria OcularRESUMO
Retinal ischemia is a common cause of many retinal diseases, leading to irreversible vision impairment and blindness. Excessive neuroinflammation, including microglial activation and T-cell responses, has been identified as a critical factor associated with neurodegeneration in retinal ischemia. Baicalein is a natural flavonoid reported to have broad anti-inflammatory and neuroprotective bioactivities. Herein, the effects of baicalein on microglia activation in vitro and in vivo were investigated. We found that baicalein exhibited robust anti-inflammatory effect on cultured human and mouse microglia, as demonstrated by decreased induction of pro-inflammatory cytokines and the phosphorylation of phosphoinositide 3-kinase (PI3K) and nuclear factor kappa B (NFκB). Proteomic analysis further unraveled baicalein's effect on modulating IL-17 signaling pathways and its upstream regulator IL-1ß. Intravitreal administration of baicalein in the mouse model of retinal ischemia/reperfusion (I/R) injury attenuated microglial activation and retinal T-cell infiltration, particularly the T helper 17 cells. Additionally, baicalein was shown to exert neuroprotective effects by significantly reducing the retinal ganglion cell (RGC) loss after I/R injury, leading to an improved retinal function and spatial vision. These results suggest that baicalein, a natural flavonoid, acts as a negative regulator of activated microglia and immune responses both in vitro and in vivo, effectively alleviating neurodegeneration in retinal I/R injury. This finding indicates that baicalein could be a potential therapeutic agent against currently incurable degenerative retinal diseases.
Assuntos
Traumatismo por Reperfusão , Doenças Retinianas , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Flavanonas , Flavonoides/farmacologia , Isquemia/metabolismo , Camundongos , Microglia/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteômica , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Doenças Retinianas/tratamento farmacológicoRESUMO
Ischemia is a common pathological condition present in many neurodegenerative diseases, including ischemic stroke, retinal vascular occlusion, diabetic retinopathy, and glaucoma, threatening the sight and lives of millions of people globally. Ischemia can trigger excessive oxidative stress, inflammation, and vascular dysfunction, leading to the disruption of tissue homeostasis and, ultimately, cell death. Current therapies are very limited and have a narrow time window for effective treatment. Thus, there is an urgent need to develop more effective therapeutic options for ischemia-induced neural injuries. With emerging reports on the pharmacological properties of natural flavonoids, these compounds present potent antioxidative, anti-inflammatory, and antiapoptotic agents for the treatment of ischemic insults. Three major active flavonoids, baicalein, baicalin, and wogonin, have been extracted from Scutellaria baicalensis Georgi (S. baicalensis); all of which are reported to have low cytotoxicity. They have been demonstrated to exert promising pharmacological capabilities in preventing cell and tissue damage. This review focuses on the therapeutic potentials of these flavonoids against ischemia-induced neurotoxicity and damage in the brain and retina. The bioactivity and bioavailability of baicalein, baicalin, and wogonin are also discussed. It is with hope that the therapeutic potential of these flavonoids can be utilized and developed as natural treatments for ischemia-induced injuries of the central nervous system (CNS).