Displaying publications 1 - 20 of 39 in total

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  1. Azhany Y, Nani D, Zunaina E
    Malays Fam Physician, 2012;7(1):43-4.
    PMID: 25606247 MyJurnal
    Matched MeSH terms: Macular Degeneration*
  2. Subramani S, Khor SE, Livingstone BI, Kulkarni UV
    Med J Malaysia, 2010 Mar;65(1):36-40.
    PMID: 21265246 MyJurnal
    To investigate the possible association between serum uric acid levels, serum C-Reactive Protein (CRP), and age-related macular degeneration (ARMD). A total 232 patients of the eye department at Hospital Tuanku Ja'afar, Negeri Sembilan, Malaysia were recruited over 9 weeks. Participants were divided into ARMD (Non-Neovascular ARMD, and Neovascular ARMD) and control groups. 107 participants with non-neovascular ARMD, 6 with neovascular ARMD, and 119 controls participated in the study. The control patients had a similar average Serum Uric Acid level to the average of all patients with ARMD (P = 0.617).
    Matched MeSH terms: Macular Degeneration/blood*; Macular Degeneration/etiology
  3. Sahak H, Saqalain M, Lott PW, McKibbin M
    Ophthalmologica, 2021;244(2):159-164.
    PMID: 33120391 DOI: 10.1159/000512636
    AIMS: To investigate the prevalence of sickle cell maculopathy (SCM), and associations with age, sex, genotype, proliferative sickle cell retinopathy (PSR) stage, and the impact on visual acuity.

    METHODS: Age, sex, and visual acuity were recorded and spectral domain OCT and ultra-wide-field images of the macula and retina were reviewed in a consecutive series of 74 adults with sickle cell disease.

    RESULTS: The median age was 37 years (range 19-73 years) and 36 cases (48.6%) were male. SCM was present in at least 1 eye of 40 cases (54.1%) or in 67 of all eyes (42.3%). SCM prevalence was 54.8%, 62.5%, and 25% for the HbSS, HbSC, and HbS/BThal or other genotypes, respectively. SCM was observed in 41 (39.4%) of the eyes with PSR stages 0, 1, and 2, and in 21 (51.2%) of the eyes with PSR stages 3, 4, and 5, respectively. Mild visual impairment or worse was present in 3 eyes (4.8%) with SCM but this was secondary to other pathology.

    CONCLUSION: SCM is a frequent finding in the eyes of adults with sickle cell disease. The prevalence is similar for the HbSS and HbSC genotypes and is not related to the PSR stage. High-contrast distance visual acuity is typically preserved.

    Matched MeSH terms: Macular Degeneration*
  4. Koh A, Lai TYY, Wei WB, Mori R, Wakiyama H, Park KH, et al.
    Retina, 2020 Aug;40(8):1529-1539.
    PMID: 31385918 DOI: 10.1097/IAE.0000000000002624
    PURPOSE: To evaluate the real-world effectiveness and safety of intravitreal ranibizumab 0.5 mg in treatment-naive patients with and without polypoidal choroidal vasculopathy (PCV).

    METHODS: Assessment of neovascular age-related macular degeneration patients with or without PCV after 12 months of ranibizumab treatment during the LUMINOUS study. Outcome measures were visual acuity and central retinal thickness changes from baseline and the rate of ocular adverse events.

    RESULTS: At baseline, 572 and 5,644 patients were diagnosed with and without PCV, respectively. The mean visual acuity gain from baseline at Month 12 in the PCV and non-PCV groups was +5.0 and +3.0 letters, respectively; these gains were achieved with a mean of 4.4 and 5.1 ranibizumab injections. Eighty percent of PCV patients and 72.2% of non-PCV patients who had baseline visual acuity ≥73 letters maintained this level of vision at Month 12; 20.6% and 17.9% of patients with baseline visual acuity <73 letters achieved visual acuity ≥73 letters in these groups. Greater reductions in central retinal thickness from baseline were also observed for the PCV group versus the non-PCV group. The rate of serious ocular adverse events was 0.7% (PCV group) and 0.9% (non-PCV group).

    CONCLUSION: LUMINOUS confirms the effectiveness and safety of ranibizumab in treatment-naive patients with PCV.

    Matched MeSH terms: Macular Degeneration
  5. Paraoan L, Sharif U, Carlsson E, Supharattanasitthi W, Mahmud NM, Kamalden TA, et al.
    Prog Retin Eye Res, 2020 11;79:100859.
    PMID: 32278708 DOI: 10.1016/j.preteyeres.2020.100859
    Secretory proteostasis integrates protein synthesis, processing, folding and trafficking pathways that are essential for efficient cellular secretion. For the retinal pigment epithelium (RPE), secretory proteostasis is of vital importance for the maintenance of the structural and functional integrity of apical (photoreceptors) and basal (Bruch's membrane/choroidal blood supply) sides of the environment it resides in. This integrity is achieved through functions governed by RPE secreted proteins, which include extracellular matrix modelling/remodelling, angiogenesis and immune response modulation. Impaired RPE secretory proteostasis affects not only the extracellular environment, but leads to intracellular protein aggregation and ER-stress with subsequent cell death. Ample recent evidence implicates dysregulated proteostasis as a key factor in the development of age-related macular degeneration (AMD), the leading cause of blindness in the developed world, and research aiming to characterise the roles of various proteins implicated in AMD-associated dysregulated proteostasis unveiled unexpected facets of the mechanisms involved in degenerative pathogenesis. This review analyses cellular processes unveiled by the study of the top 200 transcripts most abundantly expressed by the RPE/choroid in the light of the specialised secretory nature of the RPE. Functional roles of these proteins and the mechanisms of their impaired secretion, due to age and genetic-related causes, are analysed in relation to AMD development. Understanding the importance of RPE secretory proteostasis in relation to maintaining retinal health and how it becomes impaired in disease is of paramount importance for the development and assessment of future therapeutic advancements involving gene and cell therapies.
    Matched MeSH terms: Macular Degeneration/genetics; Macular Degeneration/metabolism*; Macular Degeneration/pathology
  6. Ghoshal R, Sharanjeet-Kaur S, Mohamad Fadzil N, Mutalib HA, Ghosh S, Ngah NF, et al.
    PMID: 32887214 DOI: 10.3390/ijerph17176379
    In early and intermediate age related macular degeneration (ARMD), visual acuity alone has failed to explain the complete variation of vision. The aim of the present study was to determine correlation between different visual functions and retinal morphology in eyes with early and intermediate ARMD. In this single center cross sectional study, patients diagnosed as early or intermediate ARMD in at least one eye were recruited. Visual functions measured were best- corrected distance visual acuity (DVA), near vision acuity (NVA), reading speed (RS), and contrast sensitivity (CS). Parameters such as thickness (RT) and volume (RV) of the retina, outer retinal layer thickness (ORLT) and volume (ORLV), outer nuclear layer thickness (ONLT) and volume (ONLV), retinal pigment epithelium layer-Bruch's membrane complex thickness (RPET) and volume (RPEV) were assessed employing semi-auto segmentation method of Spectralis optical coherence tomography (OCT). Twenty-six eyes were evaluated. DVA, CS, and RS showed significantly good correlation with RPET, ONLT, and ONLV, whereas NVA showed good correlation with ONLV and RPET. The present study concluded that RS, CS, NVA, and DVA represent the morphological alteration in early stages and should be tested in clinical settings. ONLT, ONLV, and RPET morphological parameters can be employed as important biomarkers in diagnosis of early to intermediate ARMD.
    Matched MeSH terms: Macular Degeneration*
  7. Pee XK, Low A, Ab Kahar MEPI, Mohamed SO, Chong YJ
    BMC Ophthalmol, 2023 Nov 07;23(1):444.
    PMID: 37932684 DOI: 10.1186/s12886-023-03186-8
    BACKGROUND: To report a rare case of pulmonary and ocular complications with visual loss due to bilateral Purtscher-like retinopathy and paracentral acute middle maculopathy (PAMM) following a hyaluronic acid (HA) filler injection to the breast. Systemic and visual recovery was attained following corticosteroid therapy.

    CASE PRESENTATION: A 27-year-old lady presented with painless blurring of vision in both eyes for 2 weeks following hyaluronic acid breast filler injections by a non-medical practitioner. She was initially admitted to the medical ward for diffuse alveolar haemorrhage and altered sensorium. The presenting visual acuity was counting fingers in both eyes. Bilateral dilated fundus examination showed hyperaemic discs, concentric rim of retinal whitening around macula with patches of polygonal-shaped retinal whitening, generalised cotton-wool spots, tortuous veins, and flame-shaped haemorrhages. Spectral-domain optical coherence tomography (SD-OCT) macula revealed hyper-reflective bands at the inner nuclear layer (INL). Fluorescein angiography demonstrated hot discs, delayed arm-to-retina time, arterial filling, and arterio-venous transit time with staining of the vessels at the posterior pole. She was managed with a tapering dose of systemic corticosteroids. The visual acuity improved to 6/12 over 8 weeks with significant anatomical and functional improvement. Dilated fundus examination showed resolution of initial funduscopy findings. The hyper-reflective bands on the OCT had resolved with subsequent thinning of the INL and disorganisation of retinal inner layers.

    CONCLUSION: Filler injections are in increasing demand and are frequently being performed by non-medical practitioners. Visual loss from non-facial HA fillers is rare. Inadvertent entry of HA into a blood vessel may potentially cause systemic and sight-threatening ocular complications. Good anatomical knowledge and proper injection technique are vital in preventing this unfortunate sequela. There are limited reports on successful visual recovery following various treatment approaches and we hope this case provides valuable insights.

    Matched MeSH terms: Macular Degeneration*
  8. Rosli, Y., Maddess, T.L., James, A.C., Goh, X.L.
    ASM Science Journal, 2009;3(1):31-37.
    MyJurnal
    Responses were recorded from normal healthy subjects and age-related macular degeneration (AMD) patients and evaluated, using a new variant of mfVEP. Subjects information was recorded using 64 EEG channels with a computer-based acquisition system. The stimulus layout was a 84 region corticallyscaled dartboard comprising 12 sectors and seven concentric rings subtending a diameter of 23º, presented dichoptically at 60 Hz. Data from the control and AMD patients were statistically compared when fitted concurrently into the multiple regression analysis. The Pattern-pulse mfVEP technique could distinguish between normal eyes and those with a definite diagnosis of dry and wet AMD when responses from the macula were considered.
    Matched MeSH terms: Wet Macular Degeneration
  9. Singh P
    Med J Malaysia, 1997 Sep;52(3):213-6.
    PMID: 10968087
    Matched MeSH terms: Macular Degeneration/etiology; Macular Degeneration/therapy
  10. Das RA, Romano A, Chiosi F, Menzione M, Rinaldi M
    Curr Drug Targets, 2011 Feb;12(2):182-9.
    PMID: 20887244
    BACKGROUND: Age-related macular degeneration (AMD) is a condition that accounts for 75% of cases of legal blindness in individuals over the age of 50.

    OBJECTIVES: The objective of this review has been to evaluate the clinical effectiveness of available combined treatments modalities in the treatment of neovascular AMD.

    DATA SOURCES: Central and Medline were searched for original research studies (Phase I, II, III), abstracts, and review articles concerning combination therapies for the control of neovascular AMD. We included randomized controlled trials (RCTs).

    RESULTS: The results of therapeutic trials focused on the actual options in the management of neovascular AMD are discussed. Intravitreal treatment with substances targeting all isotypes of vascular endothelial growth factor (VEGF) results in a significant increase in visual acuity in patients with neovascular AMD. The combination with occlusive therapies like verteporfin photodynamic therapy (V-PDT) potentially offers a reduction of re-treatment frequency rate and long-term maintenance of the benefit reached. Despite the promise from combining anti-VEGF therapies with V-PDT, other combinations to improve outcomes with V-PDT deserve attention. Corticosteroids demonstrated an antiangiogenic effect and targeted the extravascular components of CNV, such as inflammatory cells and fibrocytes. Nevertheless, the study on the clinical application of corticosteroids will require a better understanding of the potential complications. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. In AMD the goal of a combination regimen is to address the therapy toward neovascular, inflammatory, and proliferative components of the disease.

    CONCLUSIONS: Combined treatments strategies are an obvious step providing disease control when it is not achieved with a single therapeutic approach. One risk of using a single therapy to control AMD is a rebound induced by compensatory stimulation of other pathogenetic pathways. Combination therapy is a logical approach to address mechanisms of disease progression that appear to be self-sustaining once initiated.

    Matched MeSH terms: Macular Degeneration/drug therapy*; Macular Degeneration/physiopathology; Wet Macular Degeneration/drug therapy; Wet Macular Degeneration/physiopathology
  11. Cheung CM, Li X, Cheng CY, Zheng Y, Mitchell P, Wang JJ, et al.
    Ophthalmology, 2014 Aug;121(8):1598-603.
    PMID: 24661862 DOI: 10.1016/j.ophtha.2014.02.004
    To describe the prevalence and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons.
    Matched MeSH terms: Macular Degeneration/classification; Macular Degeneration/ethnology*
  12. Aslam TM, Zaki HR, Mahmood S, Ali ZC, Ahmad NA, Thorell MR, et al.
    Am J Ophthalmol, 2018 Jan;185:94-100.
    PMID: 29101008 DOI: 10.1016/j.ajo.2017.10.015
    PURPOSE: To develop a neural network for the estimation of visual acuity from optical coherence tomography (OCT) images of patients with neovascular age-related macular degeneration (AMD) and to demonstrate its use to model the impact of specific controlled OCT changes on vision.

    DESIGN: Artificial intelligence (neural network) study.

    METHODS: We assessed 1400 OCT scans of patients with neovascular AMD. Fifteen physical features for each eligible OCT, as well as patient age, were used as input data and corresponding recorded visual acuity as the target data to train, validate, and test a supervised neural network. We then applied this network to model the impact on acuity of defined OCT changes in subretinal fluid, subretinal hyperreflective material, and loss of external limiting membrane (ELM) integrity.

    RESULTS: A total of 1210 eligible OCT scans were analyzed, resulting in 1210 data points, which were each 16-dimensional. A 10-layer feed-forward neural network with 1 hidden layer of 10 neurons was trained to predict acuity and demonstrated a root mean square error of 8.2 letters for predicted compared to actual visual acuity and a mean regression coefficient of 0.85. A virtual model using this network demonstrated the relationship of visual acuity to specific, programmed changes in OCT characteristics. When ELM is intact, there is a shallow decline in acuity with increasing subretinal fluid but a much steeper decline with equivalent increasing subretinal hyperreflective material. When ELM is not intact, all visual acuities are reduced. Increasing subretinal hyperreflective material or subretinal fluid in this circumstance reduces vision further still, but with a smaller gradient than when ELM is intact.

    CONCLUSIONS: The supervised machine learning neural network developed is able to generate an estimated visual acuity value from OCT images in a population of patients with AMD. These findings should be of clinical and research interest in macular degeneration, for example in estimating visual prognosis or highlighting the importance of developing treatments targeting more visually destructive pathologies.

    Matched MeSH terms: Wet Macular Degeneration/diagnosis*; Wet Macular Degeneration/physiopathology
  13. Mohamad NA, Ramachandran V, Ismail P, Mohd Isa H, Chan YM, Ngah NF, et al.
    Genet Test Mol Biomarkers, 2017 Oct;21(10):600-607.
    PMID: 28926292 DOI: 10.1089/gtmb.2017.0079
    AIM: To determine the association of vascular endothelial growth factor (VEGF) polymorphisms with neovascular age-related macular degeneration (nAMD).

    MATERIALS AND METHODS: One hundred thirty-five nAMD patients and 135 controls were recruited to determine the association of the -460 C/T, the -2549 I/D, and the +405 G/C polymorphisms with the VEGF gene. Genotyping was conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach, and association analyses were conducted using chi-square analysis and logistic regression analysis.

    RESULTS: A significant association was observed between nAMD and the VEGF +405 G/C genotypes (p = 0.002) and alleles (odds ratio = 1.36, 95% confidence interval = 1.12-1.62, p = < 0.001) compared with the controls. This association was confirmed by logistic regression analyses, using two different genetic models (additive and dominant) resulting in p-values of p = 0.001 and p 

    Matched MeSH terms: Macular Degeneration/genetics*; Macular Degeneration/metabolism
  14. Mohamad NA, Ramachandran V, Mohd Isa H, Chan YM, Ngah NF, Ching SM, et al.
    Hum Genomics, 2019 02 22;13(1):13.
    PMID: 30795802 DOI: 10.1186/s40246-019-0197-3
    BACKGROUND: The association of HTRA1 rs11200638 and ARMS2 rs10490924 gene polymorphisms with response to intravitreal ranibizumab therapy among neovascular AMD (nAMD) subjects in Malaysia was determined in this study, followed by the expression of HTRA1 and ARMS2 genes.

    RESULTS: Both single nucleotide polymorphisms (SNPs) recorded a significant association between nAMD and controls with HTRA1 rs11200638 at P = 0.018 (OR = 1.52, 95% CI = 1.07-215) and ARMS2 rs10490924 at P 

    Matched MeSH terms: Macular Degeneration/drug therapy*; Macular Degeneration/genetics*
  15. Mookiah MR, Acharya UR, Koh JE, Chandran V, Chua CK, Tan JH, et al.
    Comput Biol Med, 2014 Oct;53:55-64.
    PMID: 25127409 DOI: 10.1016/j.compbiomed.2014.07.015
    Age-related Macular Degeneration (AMD) is one of the major causes of vision loss and blindness in ageing population. Currently, there is no cure for AMD, however early detection and subsequent treatment may prevent the severe vision loss or slow the progression of the disease. AMD can be classified into two types: dry and wet AMDs. The people with macular degeneration are mostly affected by dry AMD. Early symptoms of AMD are formation of drusen and yellow pigmentation. These lesions are identified by manual inspection of fundus images by the ophthalmologists. It is a time consuming, tiresome process, and hence an automated diagnosis of AMD screening tool can aid clinicians in their diagnosis significantly. This study proposes an automated dry AMD detection system using various entropies (Shannon, Kapur, Renyi and Yager), Higher Order Spectra (HOS) bispectra features, Fractional Dimension (FD), and Gabor wavelet features extracted from greyscale fundus images. The features are ranked using t-test, Kullback-Lieber Divergence (KLD), Chernoff Bound and Bhattacharyya Distance (CBBD), Receiver Operating Characteristics (ROC) curve-based and Wilcoxon ranking methods in order to select optimum features and classified into normal and AMD classes using Naive Bayes (NB), k-Nearest Neighbour (k-NN), Probabilistic Neural Network (PNN), Decision Tree (DT) and Support Vector Machine (SVM) classifiers. The performance of the proposed system is evaluated using private (Kasturba Medical Hospital, Manipal, India), Automated Retinal Image Analysis (ARIA) and STructured Analysis of the Retina (STARE) datasets. The proposed system yielded the highest average classification accuracies of 90.19%, 95.07% and 95% with 42, 54 and 38 optimal ranked features using SVM classifier for private, ARIA and STARE datasets respectively. This automated AMD detection system can be used for mass fundus image screening and aid clinicians by making better use of their expertise on selected images that require further examination.
    Matched MeSH terms: Macular Degeneration/diagnosis*
  16. Rosli Y, Bedford SM, James AC, Maddess T
    Vision Res, 2012 Sep 15;69:42-8.
    PMID: 22898702 DOI: 10.1016/j.visres.2012.07.019
    We compared photopic and scotopic multifocal pupillographic stimuli in age-related macular degeneration (AMD). Both eyes of 18 normal and 14 AMD subjects were tested with four stimulus variants presented at photopic and 126 times lower luminances. The multifocal stimuli presented 24 test regions/eye to the central 60°. The stimulus variants had two different check sizes, and when presented either flickered (15 Hz) for 266 ms, or were steady for 133 ms. Mean differences from normal of 5 to 7 dB were observed in the central visual field for both photopic and scotopic stimuli (all p < 0.00002). The best areas under receiver operating characteristic plots for exudative AMD in the photopic and scotopic conditions were 92.9 ± 8.0 and 90.3 ± 5.7% respectively, and in less severely affected eyes 83.8 ± 9.7% and 76.9 ± 8.2%. Damage recorded at photopic levels was possibly more diffusely distributed across the visual field. Sensitivity and specificity was similar at photopic and scotopic levels.
    Matched MeSH terms: Macular Degeneration/physiopathology*
  17. Rodrigues IA, Sprinkhuizen SM, Barthelmes D, Blumenkranz M, Cheung G, Haller J, et al.
    Am J Ophthalmol, 2016 08;168:1-12.
    PMID: 27131774 DOI: 10.1016/j.ajo.2016.04.012
    PURPOSE: To define a minimum set of outcome measures for tracking, comparing, and improving macular degeneration care.

    DESIGN: Recommendations from a working group of international experts in macular degeneration outcomes registry development and patient advocates, facilitated by the International Consortium for Health Outcomes Measurement (ICHOM).

    METHODS: Modified Delphi technique, supported by structured teleconferences, followed by online surveys to drive consensus decisions. Potential outcomes were identified through literature review of outcomes collected in existing registries and reported in major clinical trials. Outcomes were refined by the working group and selected based on impact on patients, relationship to good clinical care, and feasibility of measurement in routine clinical practice.

    RESULTS: Standardized measurement of the following outcomes is recommended: visual functioning and quality of life (distance visual acuity, mobility and independence, emotional well-being, reading and accessing information); number of treatments; complications of treatment; and disease control. Proposed data collection sources include administrative data, clinical data during routine clinical visits, and patient-reported sources annually. Recording the following clinical characteristics is recommended to enable risk adjustment: age; sex; ethnicity; smoking status; baseline visual acuity in both eyes; type of macular degeneration; presence of geographic atrophy, subretinal fibrosis, or pigment epithelial detachment; previous macular degeneration treatment; ocular comorbidities.

    CONCLUSIONS: The recommended minimum outcomes and pragmatic reporting standards should enable standardized, meaningful assessments and comparisons of macular degeneration treatment outcomes. Adoption could accelerate global improvements in standardized data gathering and reporting of patient-centered outcomes. This can facilitate informed decisions by patients and health care providers, plus allow long-term monitoring of aggregate data, ultimately improving understanding of disease progression and treatment responses.

    Matched MeSH terms: Macular Degeneration/therapy*
  18. Mookiah MR, Acharya UR, Fujita H, Koh JE, Tan JH, Noronha K, et al.
    Comput Biol Med, 2015 Aug;63:208-18.
    PMID: 26093788 DOI: 10.1016/j.compbiomed.2015.05.019
    Age-related Macular Degeneration (AMD) is an irreversible and chronic medical condition characterized by drusen, Choroidal Neovascularization (CNV) and Geographic Atrophy (GA). AMD is one of the major causes of visual loss among elderly people. It is caused by the degeneration of cells in the macula which is responsible for central vision. AMD can be dry or wet type, however dry AMD is most common. It is classified into early, intermediate and late AMD. The early detection and treatment may help one to stop the progression of the disease. Automated AMD diagnosis may reduce the screening time of the clinicians. In this work, we have introduced LCP to characterize normal and AMD classes using fundus images. Linear Configuration Coefficients (CC) and Pattern Occurrence (PO) features are extracted from fundus images. These extracted features are ranked using p-value of the t-test and fed to various supervised classifiers viz. Decision Tree (DT), Nearest Neighbour (k-NN), Naive Bayes (NB), Probabilistic Neural Network (PNN) and Support Vector Machine (SVM) to classify normal and AMD classes. The performance of the system is evaluated using both private (Kasturba Medical Hospital, Manipal, India) and public domain datasets viz. Automated Retinal Image Analysis (ARIA) and STructured Analysis of the Retina (STARE) using ten-fold cross validation. The proposed approach yielded best performance with a highest average accuracy of 97.78%, sensitivity of 98.00% and specificity of 97.50% for STARE dataset using 22 significant features. Hence, this system can be used as an aiding tool to the clinicians during mass eye screening programs to diagnose AMD.
    Matched MeSH terms: Macular Degeneration/diagnosis*
  19. Sharif U, Mahmud NM, Kay P, Yang YC, Harding SP, Grierson I, et al.
    J Cell Mol Med, 2019 01;23(1):405-416.
    PMID: 30338926 DOI: 10.1111/jcmm.13944
    The retinal pigment epithelium (RPE) plays a central role in neuroretinal homoeostasis throughout life. Altered proteolysis and inflammatory processes involving RPE contribute to the pathophysiology of age-related macular degeneration (AMD), but the link between these remains elusive. We report for the first time the effect of advanced glycation end products (AGE)-known to accumulate on the ageing RPE's underlying Bruch's membrane in situ-on both key lysosomal cathepsins and NF-κB signalling in RPE. Cathepsin L activity and NF-κB effector levels decreased significantly following 2-week AGE exposure. Chemical cathepsin L inhibition also decreased total p65 protein levels, indicating that AGE-related change of NF-κB effectors in RPE cells may be modulated by cathepsin L. However, upon TNFα stimulation, AGE-exposed cells had significantly higher ratio of phospho-p65(Ser536)/total p65 compared to non-AGEd controls, with an even higher fold increase than in the presence of cathepsin L inhibition alone. Increased proportion of active p65 indicates an AGE-related activation of NF-κB signalling in a higher proportion of cells and/or an enhanced response to TNFα. Thus, NF-κB signalling modulation in the AGEd environment, partially regulated via cathepsin L, is employed by RPE cells as a protective (para-inflammatory) mechanism but renders them more responsive to pro-inflammatory stimuli.
    Matched MeSH terms: Macular Degeneration/metabolism
  20. Mahendra CK, Tan LTH, Pusparajah P, Htar TT, Chuah LH, Lee VS, et al.
    Oxid Med Cell Longev, 2020;2020:1904178.
    PMID: 32855763 DOI: 10.1155/2020/1904178
    Retinal pigment epithelial (RPE) cells are an essential part of the human eye because they not only mediate and control the transfer of fluids and solutes but also protect the retina against photooxidative damage and renew photoreceptor cells through phagocytosis. However, their function necessitates cumulative exposure to the sun resulting in UV damage, which may lead to the development of age-related macular degeneration (AMD). Several studies have shown that UVB induces direct DNA damage and oxidative stress in RPE cells by increasing ROS and dysregulating endogenous antioxidants. Activation of different signaling pathways connected to inflammation, cell cycle arrest, and intrinsic apoptosis was reported as well. Besides that, essential functions like phagocytosis, osmoregulation, and water permeability of RPE cells were also affected. Although the melanin within RPE cells can act as a photoprotectant, this photoprotection decreases with age. Nevertheless, the changes in lens epithelium-derived growth factor (LEDGF) and autophagic activity or application of bioactive compounds from natural products can reverse the detrimental effect of UVB. Additionally, in vivo studies on the whole retina demonstrated that UVB irradiation induces gene and protein level dysregulation, indicating cellular stress and aberrations in the chromosome level. Morphological changes like retinal depigmentation and drusen formation were noted as well which is similar to the etiology of AMD, suggesting the connection of UVB damage with AMD. Therefore, future studies, which include mechanism studies via in vitro or in vivo and other potential bioactive compounds, should be pursued for a better understanding of the involvement of UVB in AMD.
    Matched MeSH terms: Macular Degeneration/pathology*
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