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Retinal aging has been recognized as a significant risk factor for various retinal disorders, including diabetic retinopathy, age-related macular degeneration, and glaucoma, following a growing understanding of the molecular underpinnings of their development. This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches, focusing on the activation of transcription factor EB. Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies, such as exercise, calorie restriction, rapamycin, and metformin, in patients and animal models of these common retinal diseases. The review critically assesses the role of transcription factor EB in retinal biology during aging, its neuroprotective effects, and its therapeutic potential for retinal disorders. The impact of transcription factor EB on retinal aging is cell-specific, influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways. In vascular endothelial cells, transcription factor EB controls important processes, including endothelial cell proliferation, endothelial tube formation, and nitric oxide levels, thereby influencing the inner blood-retinal barrier, angiogenesis, and retinal microvasculature. Additionally, transcription factor EB affects vascular smooth muscle cells, inhibiting vascular calcification and atherogenesis. In retinal pigment epithelial cells, transcription factor EB modulates functions such as autophagy, lysosomal dynamics, and clearance of the aging pigment lipofuscin, thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization. These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis, neuronal synapse plasticity, energy metabolism, microvasculature, and inflammation, ultimately offering protection against retinal aging and diseases. The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases. Therefore, it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.
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PRCIS: High perceived stress from academic pressure is associated with intraocular pressure elevation and reduced fluctuation in juvenile-onset open-angle glaucoma patients. Personalized stress assessment and relief strategies may serve as an adjunct therapy in glaucoma. OBJECTIVE: To evaluate the effect of higher perceived stress, resulting from academic pressure, on intraocular pressure (IOP) in juvenile-onset open-angle glaucoma (JOAG) patients compared to healthy individuals. PARTICIPANTS AND METHODS: The study included 48 university students aged 18 to 27, comprising 24 JOAG patients on antiglaucoma eyedrops and 24 healthy controls. In an examiner-blind pretest-posttest design, participants' IOP was measured weekly using Goldmann tonometry during three follow-up visits at the beginning and end of the academic semester. Perceived Stress Scale (PSS) scores were also evaluated at these two time points to capture the contrast in perceived stress between periods of low and high academic pressure. RESULTS: Baseline PSS score at the semester's start was lower in both groups (14.1±1.9 in glaucoma vs. 13.5±2.4 in control) and significantly increased by the end of the semester (29.2±2.1 vs. 28.5±1.3; P<0.001), indicating increased perceived stress. Concurrently, IOP rose from 22.01±5.87 mmHg to 25.08±5.84 mmHg in the glaucoma group and from 11.36±2.03 mmHg to 13.65±2.11 mmHg in the control group. Factorial analysis revealed a significant interaction between stress and JOAG [F(1,94)=15.94, P=0.001], partial η2=0.08, with stress having a greater increase on IOP in the glaucoma group (+3.10 mmHg) compared to the control group (+2.23 mmHg) [t(94)=4.457, P<0.001]. CONCLUSIONS: Higher perceived stress significantly increases IOP, especially in JOAG patients, suggesting personalised stress management as a potential adjunct therapy for patients.
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Diabetic retinopathy (DR) is a leading cause of blindness and vision impairment worldwide and represents one of the most common complications among diabetic patients. Current treatment modalities for DR, including laser photocoagulation, intravitreal injection of corticosteroid, and anti-vascular endothelial growth factor (VEGF) agents, target primarily vascular lesions. However, these approaches are invasive and have several limitations, such as potential loss of visual function, retinal scars and cataract formation, and increased risk of ocular hypertension, vitreous hemorrhage, retinal detachment, and intraocular inflammation. Recent studies have suggested mitochondrial dysfunction as a pivotal factor leading to both the vascular and neural damage in DR. Given that Coenzyme Q10 (CoQ10) is a proven mitochondrial stabilizer with antioxidative properties, this study investigated the effect of CoQ10 eyedrops [in conjunction with vitamin E d-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS)] on DR-induced neurodegeneration using a type 2 diabetes mouse model (C57BLKsJ-db/db mice). Utilizing a comprehensive electroretinography protocol, supported by immunohistochemistry, our results revealed that topical application of CoQ10 eyedrops conjugated with vitamin E TPGS produced a neuroprotective effect against diabetic-induced neurodegeneration by preserving the function and histology of various retinal neural cell types. Compared to the control group, mice treated with CoQ10 exhibited thicker outer and inner nuclear layers, higher densities of photoreceptor, cone cell, and rod-bipolar cell dendritic boutons, and reduced glial reactivity and microglial cell density. Additionally, the CoQ10 treatment significantly alleviated retinal levels of MMP-9 and enhanced mitochondrial function. These findings provide further insight into the role of mitochondrial dysfunction in the development of DR and suggest CoQ10 eyedrops, conjugated with vitamin E TPGS, as a potential complementary therapy for DR-related neuropathy.
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Background: Glaucoma is an optic neuropathy which causes irreversible vision loss. Standard perimetry, which is essential for glaucoma diagnosis, can only detect glaucomatous visual filed loss when considerable structural damage has occurred. Contrast sensitivity is one of the visual function tests that is reduced in eyes with glaucoma. It is known to be affected in pre-perimetric stages of glaucoma. Objective: The objective of this study was to investigate the discriminating ability of central contrast sensitivity perimetry in eyes with and without glaucoma. Design: The study employed a cross-sectional study design. Methods: The study participants were made of two groups; eyes diagnosed with glaucoma by an ophthalmologist based on visual field test and optical coherence tomography (OCT) and age- and sex-matched controls who were declared free from glaucoma. Static contrast sensitivity (CS) was measured in the central 10° of visual field using a custom psychophysical test. Results: There were 45 eyes with glaucoma and 45 age- and sex-matched controls in this study. The static CS in the glaucoma group was significantly reduced in 9 out of the 13 tested locations in the central 10° of the visual field. The mean static CS at 5°, 10°, superior hemifield and inferior hemifield were all significantly reduced in the glaucoma patients compared to the controls. Conclusion: Static CS measurement is a sensitive approach that can be utilized to aid in the detection of glaucoma. The use of static CS can be adopted in the development of a cost-effective yet sensitive screening tool for the detection of glaucoma.
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OBJECTIVES: Better visual performance in athletes compared to non-athletes could suggest improved macular function through physical exertion. The study aimed to investigate the effect of maximal incremental treadmill (MIT) exercise on macular function. DESIGN: An interventional study comparing the effect of maximal incremental treadmill (MIT) exercise until volitional exhaustion between athletes (nâ¯=â¯26) and non-athletes (nâ¯=â¯26). METHODS: Participants underwent an ophthalmological assessment involving repeated measurements of the photostress recovery time (PSRT) at baseline and post-exercise. PSRT was recorded after a 10-second exposure of the macular to an intense light source from an ophthalmoscope positioned 2â¯cm in front of the eye. Secondary outcome measures also recorded included the best-corrected visual acuity (BCVA) and the intraocular pressure (IOP). RESULTS: Compared to the baseline, MIT exercise markedly improved the PSRT of athletes from 42.7⯱â¯1.6â¯s to 39.6⯱â¯1.4â¯s (Pâ¯<â¯0.001), while having no significant changes in the PSRT of non-athletes. After adjusting for exercise duration, the exercise intervention showed significant effects on the PSRT improvement in the athletes compared to non-athletes after exercise [F(1,49)â¯=â¯16.941, Pâ¯<â¯0.001], with estimated marginal means of 3.00â¯s and 0.47â¯s, respectively. Also, the exercise intervention resulted in significant improvements in IOP (Pâ¯<â¯0.001) and BCVA (Pâ¯<â¯0.01) of both groups. CONCLUSIONS: MIT exercise improves macular function, BCVA, and reduced IOP in healthy athletes. Maximal incremental exercise may be recommended for competitive sports athletes seeking optimal visual performance, as long as it does not adversely impact other relevant non-visual factors.
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Exercício Físico , Pressão Intraocular , Humanos , Esforço Físico , AtletasRESUMO
Old age is associated with a greater burden of disease, including neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, as well as other chronic diseases. Coincidentally, popular lifestyle interventions, such as caloric restriction, intermittent fasting, and regular exercise, in addition to pharmacological interventions intended to protect against age-related diseases, induce transcription factor EB (TFEB) and autophagy. In this review, we summarize emerging discoveries that point to TFEB activity affecting the hallmarks of aging, including inhibiting DNA damage and epigenetic modifications, inducing autophagy and cell clearance to promote proteostasis, regulating mitochondrial quality control, linking nutrient-sensing to energy metabolism, regulating pro- and anti-inflammatory pathways, inhibiting senescence and promoting cell regenerative capacity. Furthermore, the therapeutic impact of TFEB activation on normal aging and tissue-specific disease development is assessed in the contexts of neurodegeneration and neuroplasticity, stem cell differentiation, immune responses, muscle energy adaptation, adipose tissue browning, hepatic functions, bone remodeling, and cancer. Safe and effective strategies of activating TFEB hold promise as a therapeutic strategy for multiple age-associated diseases and for extending lifespan.
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Doença de Alzheimer , Doença de Parkinson , Humanos , Autofagia/fisiologia , Doença de Parkinson/genética , Envelhecimento , Lisossomos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix BásicosRESUMO
Background: Autophagy is a conserved physiological intracellular mechanism responsible for the degradation and recycling of cytoplasmic constituents (e.g., damaged organelles, and protein aggregates) to maintain cell homeostasis. Aberrant autophagy has been observed in neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington's Disease (HD), and recently aberrant autophagy has been associated with mood disorders, such as depression. Several in vitro methods have been developed to study the complex and tightly regulated mechanisms of autophagy. In vitro methods applied to autophagy research are used to identify molecular key players involved in dysfunctional autophagy and to screen autophagy regulators with therapeutic applications in neurological diseases and mood disorders. Therefore, the aims of this narrative review are (1) to compile information on the cell-based methods used in autophagy research, (2) to discuss their application, and (3) to create a catalog of traditional and novel in vitro methods applied in neurodegenerative diseases and depression. Methods: Pubmed and Google Scholar were used to retrieve relevant in vitro studies on autophagy mechanisms in neurological diseases and depression using a combination of search terms per mechanism and disease (e.g., "macroautophagy" and "Alzheimer's disease"). A total of 37 studies were included (14 in PD, 8 in AD, 5 in ALS, 5 in %, and 5 in depression). Results: A repertoire of traditional and novel approaches and techniques was compiled and discussed. The methods used in autophagy research focused on the mechanisms of macroautophagy, microautophagy, and chaperone-mediated autophagy. The in vitro tools presented in this review can be applied to explore pathophysiological mechanisms at a molecular level and to screen for potential therapeutic agents and their mechanism of action, which can be of great importance to understanding disease biology and potential therapeutic options in the context of neurodegenerative disorders and depression. Conclusion: This is the first review to compile, discuss, and provide a catalog of traditional and novel in vitro models applied to neurodegenerative disorders and depression.
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CLINICAL RELEVANCE: Inclusion of personality profile assessment and appropriate psychotherapeutic regimen in glaucoma diagnosis and management protocols could prove useful for enhanced medication adherence in patients living with glaucoma. BACKGROUND: There is poor adherence to medication among patients with glaucoma, especially in people of African ancestry. The present study assessed the influence of personality traits on adherence to glaucoma medication among patients living with primary open-angle glaucoma (POAG) from an African population. METHODS: A clinic-based cross-sectional study was conducted among patients with POAG attending a specialist eye-care facility. Adapted and validated questionnaires for personality trait (The Big Five Inventory) and medication adherence (Medication Adherence Report Scale 5) were used. RESULTS: Self-reported adherence to glaucoma medication was 60.8%. The personality traits conscientiousness and agreeableness significantly predicted medication adherence but accounted for only 30.3% and 13.3% of the variance, respectively. Non-adherence to glaucoma medication was significantly predicted by the personality profiles neuroticism, extraversion and openness which, respectively, accounted for 61.7%, 20.3% and 13.3% of the variance in the personality trait assessment. Old age and longer use of glaucoma medications were also significantly associated with non-adherence to glaucoma medication. CONCLUSIONS: Personality trait dimensions were significantly associated with glaucoma medication adherence in this at-risk population.
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Glaucoma de Ângulo Aberto , Humanos , Estudos Transversais , Glaucoma de Ângulo Aberto/tratamento farmacológico , Personalidade , Adesão à Medicação , Inventário de PersonalidadeRESUMO
The study investigated the differential response to a single bout of maximal incremental treadmill exercise between athletes and non-athletes without dry eyes regarding tear secretion, tear film stability, visual acuity (VA), and stereoacuity. Additionally, the study examined the effect of gender and the duration of exercise on exercise-induced changes. Study participants included young university students aged 18-25 years who were athletes (male/female: 13/13) or non-athletes (male/female: 17/9). Participants underwent an aerobic exercise session using a treadmill and following the laid down Bruce treadmill test protocol till exhaustion. Measurements were taken in the order of distance VA, stereopsis, non-invasive tear break-up time (TBUT), and phenol red thread test, at baseline and after the exercise regimen. Within- and between-subject analyses using multiple t-tests with correction for multiple comparisons were performed to determine differences before and after exercise in athletes and non-athletes. Subsequently, ANCOVA was used to assess the influence of gender and the duration of exercise. The mean age (SD) of the athletes and the non-athletes was 22.4 ± 2.1 years and 21.8 ± 2.1 years, respectively (p = 0.357). Before exercise, the athletes had higher TBUT than non-athletes (14.6 ± 2.9 s vs. 11.9 ± 3.8 s; p = 0.021), but no difference was observed in any other ocular measurements. After exercise, the athletes showed significant improvement in tear secretion with the basal tear secretion increasing from 22.3 ± 2.5 mm to 25.8 ± 1.7 mm (p < 0.001). The non-athletes on the other hand had a borderline increase in tear secretion from 21.42 ± 2.85 mm to 23.73 ± 2.68 mm (p = 0.08). Also, the TBUT was much improved in the athletes after exercise compared to the non-athletes (17.7 ± 2.7 s vs. 14.8 ± 2.9 s, p = 0.004). Additionally, exercise improved the VA indifferently between the groups, while stereoacuity was unchanged after exercise in either group. Gender had no influence on the differences in the tear function measures between athletes and non-athletes after exercise. The duration of exercise, however, showed a borderline effect on the tear film stability (p = 0.068) after exercise. Our findings support the differential effect of maximal incremental treadmill exercise on tear secretion and tear film stability between athletes and non-athletes. Thus, increased physical fitness and the duration of exercise might be crucial in the improvement of tear function through aerobic exercise.
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Atletas , Exercício Físico/fisiologia , Lágrimas/fisiologia , Adolescente , Adulto , Percepção de Profundidade/fisiologia , Síndromes do Olho Seco/fisiopatologia , Teste de Esforço , Feminino , Humanos , Masculino , Fatores Sexuais , Acuidade Visual/fisiologia , Adulto JovemRESUMO
In age-related macular degeneration (AMD), hydroquinone (HQ)-induced oxidative damage in retinal pigment epithelium (RPE) is believed to be an early event contributing to dysregulation of inflammatory cytokines and vascular endothelial growth factor (VEGF) homeostasis. However, the roles of antioxidant mechanisms, such as autophagy and the ubiquitin-proteasome system, in modulating HQ-induced oxidative damage in RPE is not well-understood. This study utilized an in-vitro AMD model involving the incubation of human RPE cells (ARPE-19) with HQ. In comparison to hydrogen peroxide (H2O2), HQ induced fewer reactive oxygen species (ROS) but more oxidative damage as characterized by protein carbonyl levels, mitochondrial dysfunction, and the loss of cell viability. HQ blocked the autophagy flux and increased proteasome activity, whereas H2O2 did the opposite. Moreover, the lysosomal membrane-stabilizing protein LAMP2 and cathepsin D levels declined with HQ exposure, suggesting loss of lysosomal membrane integrity and function. Accordingly, HQ induced lysosomal alkalization, thereby compromising the acidic pH needed for optimal lysosomal degradation. Pretreatment with MG132, a proteasome inhibitor and lysosomal stabilizer, upregulated LAMP2 and autophagy and prevented HQ-induced oxidative damage in wildtype RPE cells but not cells transfected with shRNA against ATG5. This study demonstrated that lysosomal dysfunction underlies autophagy defects and oxidative damage induced by HQ in human RPE cells and supports lysosomal stabilization with the proteasome inhibitor MG132 as a potential remedy for oxidative damage in RPE and AMD.
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Autofagia , Lisossomos/metabolismo , Degeneração Macular/etiologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Catepsina D/metabolismo , Células Cultivadas , Humanos , Hidroquinonas , Leupeptinas , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Degeneração Macular/metabolismo , Mitocôndrias/metabolismo , Epitélio Pigmentado da Retina/citologiaRESUMO
PURPOSE: The purpose of this study was to investigate the utility of two ocular biometric measurements to obtain Hirschberg ratios (HRs) in a binocularly normal paediatric population, and to assess the repeatability of this approach. METHODS: Ocular biometry data from 80 participants (aged 5 to 14 years) was obtained using the KM-1 LED manual keratometer and the Tomey Biometer AL-100 A-scan. HRs were calculated from corneal curvature and anterior chamber depth measurements in the horizontal and vertical meridians of each eye using a regression equation based on a geometric optics model. To assess intrasubject variability in the HRs obtained from biometry, measurements were repeated approximately 1 h later. RESULTS: At the initial measurement, mean (SD, range) HRs were 10.77 (0.79, 9.14-12.73) and 11.02 (0.82, 9.48-13.32) °/mm for the horizontal and vertical meridians, respectively. There was a significant difference between the horizontal and vertical HRs (p < 0.0001). Mean intrasubject variability of HR was 0.06 °/mm (95% Limit of Agreement [LOA]: -0.82 to 0.94 °/mm), and 0.05 °/mm (95% LOA: -1.05 to 1.15 °/mm) for the horizontal and vertical meridians, respectively. CONCLUSION: The results indicated that HRs obtained through ocular biometry in a binocularly normal paediatric population are consistent with previous studies in both strabismic children and adult cohorts. The HRs obtained with this technique were highly repeatable in this study population. This approach to gaze position calibration could be used in lieu of other empirical techniques in children.
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Câmara Anterior , Biometria , Adulto , Calibragem , Criança , Córnea , Humanos , Óptica e Fotônica , Reprodutibilidade dos TestesRESUMO
PURPOSE: To evaluate the impact of blood sugar level on ocular measures, including refractive error (RE), amplitude of accommodation (AoA), and lag of accommodation (LoA), in pre-presbyopes with type-1 diabetes. METHOD: The fasting blood sugar (FBS) and ocular measures of type-1 diabetes patients (age: 14-39 years; n = 30) on insulin treatment was recorded while they fasted on two separate visits, at baseline and 3 months later. The AoA and LoA was measured with the appropriate spectacle correction worn. The Welch's t-test was used for comparison of the baseline measures between the normal FBS ≤ 7 (n = 10) and higher FBS > 7 (n = 20) patients, and the paired t-test used to investigate for differences between the baseline and follow-up data in patients with changes in FBS. RESULTS: On average, the spectacle correction for the normal FBS group was marginally more myopic (RE: -0.30 ± 0.67 D vs. +0.18 ± 1.00 D, p = 0.032), and they showed greater AoA (5.38 ± 1.08 D vs. 3.68 ± 1.43 D, p < 0.001) and lower LoA (1.00 ± 0.30 D vs. 1.30 ± 0.38 D, p = 0.004) compared with the higher FBS group at baseline. On the follow-up visit attended by 25 patients, the FBS of 15 patients was reduced by an average of 7.0 mmol/L, 8 patients had an average increase of 5.2 mmol/L, while 2 patients recorded no changes relative to the baseline. The patients whose FBS was reduced showed improvement in the mean AoA from 3.78 ± 1.58 D to 4.88 ± 1.61 D (p < 0.001) and a reduction in the mean LoA from 1.37 ± 0.40D to 0.87 ± 0.19D (p < 0.001), whereas those with deteriorated control of the FBS showed an opposite trend. CONCLUSIONS: Controlling hyperglycemia improves ocular accommodation in type-1 diabetes.
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Diabetes Mellitus Tipo 1 , Miopia , Acomodação Ocular , Adolescente , Adulto , Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Óculos , Humanos , Refração Ocular , Adulto JovemRESUMO
BACKGROUND: Autophagy has a crucial role in the defense against parasites. The interplay existing between host autophagy and parasites has varied outcomes due to the kind of host cell and microorganism. The presence of autophagic compartments disrupt a significant number of pathogens and are further cleared by xenophagy in an autolysosome. Another section of pathogens have the capacity to outwit the autophagic pathway to their own advantage. RESULT: To comprehend the interaction between pathogens and the host cells, it is significant to distinguish between starvation-induced autophagy and other autophagic pathways. Subversion of host autophagy by parasites is likely due to differences in cellular pathways from those of 'classical' autophagy and that they are controlled by parasites in a peculiar way. In xenophagy clearance at the intracellular level, the pathogens are first ubiquitinated before autophagy receptors acknowledgement, followed by labeling with light chain 3 (LC3) protein. The LC3 in LC3-associated phagocytosis (LAP) is added directly into vacuole membrane and functions regardless of the ULK, an initiation complex. The activation of the ULK complex composed of ATG13, FIP200 and ATG101causes the initiation of host autophagic response. Again, the recognition of PAMPs by conserved PRRs marks the first line of defense against pathogens, involving Toll-like receptors (TLRs). These all important immune-related receptors have been reported recently to regulate autophagy. CONCLUSION: In this review, we sum up recent advances in autophagy to acknowledge and understand the interplay between host and parasites, focusing on target proteins for the design of therapeutic drugs. The target host proteins on the initiation of the ULK complex and PRRs-mediated recognition of PAMPs may provide strong potential for the design of therapeutic drugs against parasitic infections.
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Trehalose is a natural dietary molecule that has shown antiaging and neuroprotective effects in several animal models of neurodegenerative diseases. The role of trehalose in the management of age-related macular degeneration (AMD) is yet to be investigated and whether trehalose could be a remedy for the treatment of diseases linked to oxidative stress and NRF2 dysregulation. Here, we showed that incubation of human retinal pigment epithelial (RPE) cells with trehalose enhanced the mRNA and protein expressions of TFEB, autophagy genes ATG5 and ATG7, as well as protein expressions of macroautophagy markers, LC3B and p62/SQTM1, and the chaperone-mediated autophagy (CMA) receptor LAMP2. Cathepsin D, a hydrolytic lysosomal enzyme, was also increased by trehalose, indicating higher proteolytic activity. Moreover, trehalose upregulated autophagy flux evident by an increase in the endogenous LC3B level, and accumulation of GFP-LC3B puncta and free GFP fragments in GFP-LC3 - expressing cells in the presence of chloroquine. In addition, the mRNA levels of key molecular targets implicated in RPE damage and AMD, such as vascular endothelial growth factor- (VEGF-) A and heat shock protein 27 (HSP27), were downregulated, whereas NRF2 was upregulated by trehalose. Subsequently, we mimicked in vitro AMD conditions using hydroquinone (HQ) as the oxidative insult on RPE cells and evaluated the cytoprotective effect of trehalose compared to vehicle treatment. HQ depleted NRF2, increased oxidative stress, and reduced the viability of cells, while trehalose pretreatment protected against HQ-induced toxicity. The cytoprotection by trehalose was dependent on autophagy but not NRF2 activation, since autophagy inhibition by shRNA knockdown of ATG5 led to a loss of the protective effect. The results support the transcriptional upregulation of TFEB and autophagy by trehalose and its protection against HQ-induced oxidative damage in RPE cells. Further investigation is, therefore, warranted into the therapeutic value of trehalose in alleviating AMD and retinal diseases associated with impaired NRF2 antioxidant defense.
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Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Epitélio Pigmentado da Retina/metabolismo , Trealose/uso terapêutico , Animais , Autofagia , Modelos Animais de Doenças , Humanos , Estresse Oxidativo/efeitos dos fármacos , Trealose/farmacologia , Regulação para CimaRESUMO
Age-related macular degeneration (AMD) is a common cause of visual impairment in the elderly. There are very limited therapeutic options for AMD with the predominant therapies targeting vascular endothelial growth factor (VEGF) in the retina of patients afflicted with wet AMD. Hence, it is important to remind readers, especially those interested in AMD, about current studies that may help to develop novel therapies for other stages of AMD. This study, therefore, provides a comprehensive review of studies on human specimens as well as rodent models of the disease, to identify and analyze the molecular mechanisms behind AMD development and progression. The evaluation of this information highlights the central role that oxidative damage in the retina plays in contributing to major pathways, including inflammation and angiogenesis, found in the AMD phenotype. Following on the debate of oxidative stress as the earliest injury in the AMD pathogenesis, we demonstrated how the targeting of oxidative stress-associated pathways, such as autophagy and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, might be the futuristic direction to explore in the search of an effective treatment for AMD, as the dysregulation of these mechanisms is crucial to oxidative injury in the retina. In addition, animal models of AMD have been discussed in great detail, with their strengths and pitfalls included, to assist inform in the selection of suitable models for investigating any of the molecular mechanisms.
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Degeneração Macular/metabolismo , Estresse Oxidativo/fisiologia , Animais , Modelos Animais de Doenças , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Inter-regional trends of visual loss in most developing countries remain largely unknown. We compared the causes of childhood blindness among children attending blind schools in the northern (one school) and southern (two schools) regions of Ghana and assessed their need for spectacles and low-vision devices. METHODS: Using a standardised methodology, children were examined by an ophthalmologist and optometrists in each location. Causes of visual loss were classified anatomically and by time of onset, and avoidable causes identified. Children identified with functional low vision were assessed and provided with low-vision devices. RESULTS: A total of 252 children under 16 years of age were examined in the schools. The overall prevalence of total blindness was 73 (29.0 per cent), with similar proportions (p = 0.87) in the north (29 [28.4 per cent]) and south (44 [29.3 per cent]); 92 (36.5 per cent) had functional low vision. Two children improved with spectacles and 35 benefited from low-vision devices. Corneal scarring was significantly (p = 0.045) more prevalent in southern Ghana (n = 150) than in the north (n = 102), responsible for visual loss in 36 (24.0 per cent, 95% CI 17.2-30.8 per cent) and 14 (13.7 per cent, 95% CI 7.0-20.4 per cent) cases, respectively. No significant difference (p = 0.321) was observed in the prevalence of cataract between northern (28: 27.5 per cent, 95% CI 18.3-36.2 per cent) and southern Ghana (33: 22.0 per cent, 95% CI 15.4-28.6 per cent). Over 87 per cent of children had 'avoidable' causes of visual loss, with a higher proportion being treatable (124: 49.2 per cent) than preventable (96: 38 per cent). CONCLUSION: Cataract was the major cause of visual loss in the overall population. The south had a higher proportion of corneal scarring and late-onset blindness compared with the north. More than one-third of blindness in blind schools in Ghana could have been prevented by primary care interventions and nearly half could have been treated surgically to prevent visual loss. Two in five children in blind schools in Ghana could benefit from optical intervention.
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Cegueira/epidemiologia , Instituições Acadêmicas , Baixa Visão/epidemiologia , Pessoas com Deficiência Visual/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Gana/epidemiologia , Humanos , Masculino , Prevalência , Estudos Prospectivos , Acuidade VisualRESUMO
SIGNIFICANCE: Self-adjustable spectacles are increasingly being used in refractive service delivery programs in developing countries. Despite the success of self-refraction as a refraction technique, compliance with actual wear of adjustable spectacles has not been evaluated. Findings in this study have significant programmatic implications for the effectiveness and sustainability of this mode of correction in developing countries. PURPOSE: The purpose of this study was to assess compliance with wearing of adjustable spectacles and factors associated with compliance in pre-teen schoolchildren at 6 months after spectacles were dispensed. METHODS: A cohort of 86 children aged 6 to 12 years with presenting vision worse than or equal to 6/12 in the better eye that could be improved to better than or equal to 6/7.5 by subjective refraction and who were identified from a randomized sample of 18 primary schools in the coastal areas of Cape Coast in Ghana received free FocusSpecs adjustable spectacles after successfully completing self-refraction and cycloplegic subjective refraction. Follow-up examination to assess compliance and to determine reasons for noncompliance was conducted at 6 months after spectacle provision. Logistic regression models assessed factors associated with spectacle wear compliance (95% confidence intervals [CIs]). RESULTS: Spectacle wear compliance was 33.7% (95% CI, 31.3 to 36.1%); an additional 29% had their spectacles with them but were not wearing them. The major reasons given by the children for noncompliance were "loss" (32%; 18/57) and "breakage" (23%; 13/57). Modest compliance (49%) was observed among the poorer children who attend public schools. Attending public school was the only predictor of compliance to spectacle wear (odds ratio, 3.096; 95% CI, 1.228 to 7.805; P = .02). CONCLUSIONS: Despite accurate self-refraction by most children, only a small proportion was compliant with actual wear of the spectacles. Loss and breakage were the major reasons for noncompliance. The poorer children who attend public schools, who stand to benefit most from the technology, were the ones more likely to be compliant with wear.
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Óculos , Cooperação do Paciente/estatística & dados numéricos , Erros de Refração/terapia , População Rural/estatística & dados numéricos , Criança , Estudos Transversais , Óculos/estatística & dados numéricos , Feminino , Gana/epidemiologia , Humanos , Modelos Logísticos , Masculino , Razão de Chances , Refração Ocular/fisiologia , Erros de Refração/diagnóstico , Erros de Refração/fisiopatologia , Serviços de Saúde Escolar , Instituições Acadêmicas , Inquéritos e Questionários , Testes Visuais , Acuidade Visual/fisiologiaRESUMO
PURPOSE: To determine the near vision spectacle coverage and barriers to obtaining near vision correction among adults aged 35 years and older in the Cape Coast Metropolis of Ghana. METHODS: A population-based cross-sectional study design was adopted and 500 out of 576 participants aged 35 years and older were examined from 12 randomly selected clusters in Cape Coast, Ghana. All participants underwent a comprehensive eye examination which included: distance and near visual acuities measurements and external and internal ocular health assessments. Distance and near refractions were performed using subjective refraction technique. Information on participants' demographics, near vision correction status, near visual needs and barriers to acquiring near vision correction were obtained through a questionnaire administered as part of the study. RESULTS: The mean age of participants was 52.3±10.3 years of whom 280 (56%) were females and 220 (44%) were males. The near vision spectacle coverage was 25%, 33% "met need" for near vision correction in the presbyopic population, and 64% unmet need in the entire study population. After controlling for other variables, age (5th and 6th decades) and educational level were associated with "met need" for near vision correction (OR=2.7 (1.55-4.68), p =0.00, and OR=2.36 (1.18-4.72), p=0.02 respectively). Among those who needed but did not have near vision correction, 64 (26%) did not feel the need for correction, 55 (22%) stated that they were unaware of available interventions, and 53 (21%) found the cost of near vision correction prohibitive. CONCLUSION: There was a low near vision spectacle coverage in this population which suggests the need for strategies on health education and promotion to address the lack of awareness of spectacle need and cost of services.
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Óculos/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Miopia/terapia , Presbiopia/terapia , Adulto , Idoso , Estudos Transversais , Escolaridade , Feminino , Gana , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Despite findings that contact lens wear for vision correction provides better quality of life than spectacles, contact lens use in developing countries is low. This study evaluated knowledge, usage and barriers associated with contact lens wear among spectacle wearers in Cape Coast, Ghana. METHOD: A cross-sectional survey using a structured questionnaire was conducted on an adult population of spectacle wearers to assess their knowledge of contact lens wear for vision correction. The participants were proportionately sampled from three eye clinics in the Cape Coast Metropolis, Ghana. Questionnaires were either self-administered or completed with the help of a research assistant. RESULTS: Of the 422 participants, only 147 (34.8%) knew of contact lens wear for vision correction. The proportion of spectacle wearers reporting history of contact lens wear was 14 (3.3%). Barriers to contact lens wear reported were satisfaction with vision through spectacles 102 (25.0%), lack of adequate information 111 (27.2%), fear of side effects 94 (23.0%) and cost 78 (19.1%). The younger adults and those with higher number of changes of spectacles were more likely to know of contact lenses. CONCLUSION: Knowledge and usage of contact lenses among spectacle wearers was low. Contact lens education and demonstration of visual performance through fitting of trial contact lenses on potential candidates may help overcome barriers to contact lens wear.
Assuntos
Lentes de Contato/estatística & dados numéricos , Países em Desenvolvimento , Conhecimentos, Atitudes e Prática em Saúde , Erros de Refração/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Gana , Acessibilidade aos Serviços de Saúde , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Qualidade de Vida , Inquéritos e Questionários , Acuidade VisualRESUMO
PURPOSE: To determine the prevalence and causes of visual impairment and blindness among cocoa farmers in Ghana in order to formulate early intervention strategies. METHODS: A cross-sectional study using multistage random sampling from four cocoa growing districts in Ghana was conducted from November 2013 to April 2014. A total of 512 cocoa farmers aged 40 years and older were interviewed and examined. The brief interview questionnaire was administered to elicit information on the demographics and socioeconomic details of participants. The examination included assessment of visual acuity (VA), retinoscopy, subjective refraction, direct ophthalmoscopy, slit-lamp biomicroscopy and intraocular pressure (IOP). For quality assurance, a random sample of cocoa farmers were selected and re-examined independently. RESULTS: Moderate to severe visual impairment (VA <6/18 to 3/60 in the better-seeing eye) was present in 89 participants (17.4%) and 27 (5.3%) were blind (presenting VA <3/60 in the better eye) defined using presenting VA. The main causes of visual impairment were cataract (45, 38.8%), uncorrected refractive error (42, 36.2%), posterior segment disorders (15, 12.9%), and corneal opacity (11, 9.5%). CONCLUSION: The prevalence of visual impairment and blindness among cocoa farmers in Ghana is relatively high. The major causes of visual impairment and blindness are largely preventable or treatable, indicating the need for early eye care service interventions.