Parallelism for Quantitative Image Analysis of Photoreceptor–Retinal Pigment Epithelium Complex Alterations in Diabetic Macular Edema

Objectives Diabetic macular edema (DME) is a complication of diabetes mellitus that leads to diabetic retinopathy. Thus far, the role of serum exosomal microRNAs (miRNAs) in DME progression remains elusive. This study investigated serum exosomal miRNAs from patients with type 2 diabetes (T2D) and DME to identify miRNAs associated with expression of vascular endothelial growth factor (VEGF), a pivotal component in DME progression; it also evaluated the diagnostic values of these miRNAs for DME. Methods Serum was collected from patients with T2D who did (n = 20) and did not have DME (n = 24). Exosomes were isolated from serum and subjected to real-time polymerase chain reaction, western blotting, luciferase reporter, and miRNA profiling analyses. Results VEGF was significantly upregulated in ARPE-19 cells treated with exosomes from patients with T2D and DME, compared with exosomes from patients with T2D alone. Among the top 10 downregulated miRNAs identified during exosomal miRNA profiling, miR-377-3p inhibited the expression of VEGF. Luciferase reporter assays confirmed that miR-377-3p could directly regulate VEGF expression. Receiver operating characteristic analysis identified serum exosomal miR-377-3p as a potential biomarker for DME. Conclusion Serum exosomal miR-377-3p inhibits VEGF expression to suppress retinal pigment epithelium proliferation and offers a diagnostic biomarker for DME.

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Impaired retinal pigment epithelium in paclitaxel-induced macular edema

Medicine ◽

10.1097/md.0000000000011229 ◽

2018 ◽

Vol 97 (26) ◽

pp. e11229 ◽

Cited By ~ 9

Author(s):

Chia-Hsin Shih ◽

Yuan-Chieh Lee

Keyword(s):

Retinal Pigment Epithelium ◽

Macular Edema ◽

Pigment Epithelium ◽

Retinal Pigment

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Relationship between Outer Retinal Layers Thickness and Visual Acuity in Diabetic Macular Edema

BioMed Research International ◽

10.1155/2015/981471 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Raymond L. M. Wong ◽

Jacky W. Y. Lee ◽

Gordon S. K. Yau ◽

Ian Y. H. Wong

Keyword(s):

Visual Acuity ◽

Macular Edema ◽

Correlation Coefficient ◽

Diabetic Macular Edema ◽

Retinal Thickness ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Retinal Layers ◽

Snellen Chart ◽

Foveal Center

Purpose. To investigate the correlation of outer retinal layers (ORL) thickness and visual acuity (VA) in patients with diabetic macular edema (DME).Methods. Consecutive DME patients seen at the Retina Clinic of The University of Hong Kong were recruited for OCT assessment. The ORL thickness was defined as the distance between external limiting membrane (ELM) and retinal pigment epithelium (RPE) at the foveal center. The correlation between total retinal thickness, ORL thickness, and vision was calculated.Results. 78 patients with DME were recruited. The mean age was 58.1 years (±11.5 years) and their mean visual acuity measured with Snellen chart was 0.51 (±0.18). The correlation coefficient between total retinal thickness and visual acuity was 0.34 (P< 0.001) whereas the correlation coefficient was 0.65 between ORL thickness and visual acuity (P< 0.001).Conclusion. ORL thickness correlates better with vision than the total retinal thickness. It is a novel OCT parameter in the assessment of DME. Moreover, it could be a potential long term visual prognostic factor for patients with DME.

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Aqueous humour concentrations of PEDF and Erythropoietin are not influenced by subthreshold micropulse laser treatment of diabetic macular edema

Bioscience Reports ◽

10.1042/bsr20190328 ◽

2019 ◽

Vol 39 (6) ◽

Cited By ~ 1

Author(s):

Edoardo Midena ◽

Silvia Bini ◽

Luisa Frizziero ◽

Elisabetta Pilotto ◽

Graziana Esposito ◽

...

Keyword(s):

Macular Edema ◽

Diabetic Macular Edema ◽

Aqueous Humour ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Future Research ◽

Micropulse Laser ◽

Subthreshold Micropulse Laser ◽

Treatment Naïve ◽

Glass Chip

Abstract Purpose: To determine if aqueous humour (AH) concentrations of Retinal Pigment Epithelium (RPE)’s biomarkers are modified after subthreshold micropulse laser (SMPL) treatment of diabetic macular edema (DME). Methods: Naïve DME and healthy subjects were enrolled. All DME patients received SMPL treatments (577-nm yellow light, 5% duty cycle of 0.2 s, power 250 mW), according to study protocol. AH of DME eyes was sampled at baseline and periodically after first SMPL treatment. Control eyes were sampled before cataract surgery. Pigment Epithelium Derived Factor (PEDF) and Erythropoietin (EPO) were quantified with glass-chip protein array. Results: Eighteen DME patients (central retinal thickness ≤ 400 μm on Spectral Domain Optical Coherence Tomography (SD-OCT)) and ten controls were enrolled. The main exclusion criteria were high refractive error, proliferative diabetic retinopathy, glaucoma and neurodegenerative disorders. PEDF concentration was decreased in DME patients at baseline versus controls (P=0.012), while EPO was increased (P=0.029). Both molecules’ concentrations remained stable during follow-up after treatments, compared with DME-baseline. Conclusions: The AH concentrations of RPE biomarkers were significantly different in DME treatment-naïve eyes versus controls. The expression of PEDF and EPO remained unchanged after treatments with SMPL in DME eyes. These data are relevant for future research and applications of SMPL.

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Significance of Hyperreflective Foci as an Optical Coherence Tomography Biomarker in Retinal Diseases: Characterization and Clinical Implications

Journal of Ophthalmology ◽

10.1155/2021/6096017 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Serena Fragiotta ◽

Solmaz Abdolrahimzadeh ◽

Rosa Dolz-Marco ◽

Yoichi Sakurada ◽

Orly Gal-Or ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Macular Edema ◽

Diabetic Macular Edema ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Age Related Macular Degeneration ◽

Retinal Diseases ◽

Optical Coherence ◽

Hyperreflective Foci ◽

Age Related

Hyperreflective foci (HRF) is a term coined to depict hyperreflective dots or roundish lesions within retinal layers visualized through optical coherence tomography (OCT). Histopathological correlates of HRF are not univocal, spacing from migrating retinal pigment epithelium cells, lipid-laden macrophages, microglial cells, and extravasated proteinaceous or lipid material. Despite this, HRF can be considered OCT biomarkers for disease progression, treatment response, and prognosis in several retinal diseases, including diabetic macular edema, age-related macular degeneration (AMD), retinal vascular occlusions, and inherited retinal dystrophies. The structural features and topographic location of HRF guide the interpretation of their significance in different pathological conditions. The presence of HRF less than 30 μm with reflectivity comparable to the retinal nerve fiber layer in the absence of posterior shadowing in diabetic macular edema indicates an inflammatory phenotype with a better response to steroidal treatment. In AMD, HRF overlying drusen are associated with the development of macular neovascularization, while parafoveal drusen and HRF predispose to macular atrophy. Thus, HRF can be considered a key biomarker in several common retinal diseases. Their recognition and critical interpretation via multimodal imaging are vital to support clinical strategies and management.

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The role of inflammation and neurodegeneration in diabetic macular edema

Therapeutic Advances in Ophthalmology ◽

10.1177/25158414211055963 ◽

2021 ◽

Vol 13 ◽

pp. 251584142110559

Author(s):

Vincenzo Starace ◽

Marco Battista ◽

Maria Brambati ◽

Michele Cavalleri ◽

Federico Bertuzzi ◽

...

Keyword(s):

Macular Edema ◽

Diabetic Macular Edema ◽

Ganglion Cells ◽

Vascular Dysfunction ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Retinal Ganglion ◽

High Blood Glucose ◽

Oxidation Stress ◽

Antiangiogenic Drugs

The pathogenesis of diabetic macular edema (DME) is complex. Persistently high blood glucose activates multiple cellular pathways and induces inflammation, oxidation stress, and vascular dysfunction. Retinal ganglion cells, macroglial and microglial cells, endothelial cells, pericytes, and retinal pigment epithelium cells are involved. Neurodegeneration, characterized by dysfunction or apoptotic loss of retinal neurons, occurs early and independently from the vascular alterations. Despite the increasing knowledge on the pathways involved in DME, only limited therapeutic strategies are available. Besides antiangiogenic drugs and intravitreal corticosteroids, alternative therapeutic options tackling inflammation, oxidative stress, and neurodegeneration have been considered, but none of them has been currently approved.

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VISUAL OUTCOME IN DIABETIC MACULAR EDEMA AFTER GRID LASER TREATMENT

The Professional Medical Journal ◽

10.29309/tpmj/2016.23.04.1516 ◽

2016 ◽

Vol 23 (04) ◽

pp. 478-483

Author(s):

Muhmmad Jameel Shahid ◽

Faheem Ahmad ◽

Muhammad Asif ◽

Muhmmad Nabeel Sultan

Keyword(s):

Diabetic Retinopathy ◽

Macular Edema ◽

Diabetic Macular Edema ◽

Laser Photocoagulation ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Case Series ◽

Visual Outcome ◽

Blood Retinal Barrier ◽

Department Of Ophthalmology

Regarding the causes of blindness, Diabetic retinopathy is a one the majorcause of blindness in all types persons from both industrialized and developing countries.Due to inadequate eating habits, prevalence of diabetic retinopathy is increasing. Both focaland diffuse leakage from retinal capillaries can cause Diabetic macular edema. Varioustreatment modalities for macular photocoagulation are focal laser, Grid laser and modified gridused in patients having diabetic macular edema Study Design: Prospective, interventional,noncompetitive case series. Setting: Department of Ophthalmology, Allied Hospital andDepartment of Ophthalmology, Divisional Headquarter Hospital Faisalabad. Period: One yearfrom April 2012 to April 2013. Materials and Methods: A total of 200 eyes of 200 patientswith clinical significant macular edema that met the inclusion criteria were enrolled. Results: Inthis study, 200 patients with diabetic macular edema were studied. Of these 121 (60.5%) weremales and 79 (39.5%) females with mean age of 38.52 years (SD 7.512, Range 25-50 years).All patients had diffuse, clinically significant macular edema at baseline for which they hadreceived grid laser photocoagulation. Discussion: In recent past number of diabetic patientsall over the world has increased that has caused increase incident of diabetic retinopathy .Soin patients having diabetic retinopathy, macular edema can cause deterioration in visual acuityduring any stage of diabetic retinopathy. The pathogenesis of Diabetic macular edema (DME)is the disruption of inner blood – retinal barrier that is known to be associated with metabolicalteration affecting the retinal pigment epithelium or retinal vascular endothelium. Focal and/orgrid laser photocoagulation is being considered as the treatment of DME. Conclusion: Macularphotocoagulation was found to be an effective method of treatment for CSME among diabeticpatients, which has resulted in a positive visual outcome in 87% of the patients (stable andimproved vision).

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Combination of intravitreal injections of ranibizumab and selective laser coagulation of retinal pigment epithelium in the treatment of diabetic cystoid macular edema

Oftalmologicheskii Zhurnal ◽

10.31288/oftalmolzh201331822 ◽

2013 ◽

Vol 43 (3) ◽

pp. 18-22

Author(s):

N. Umanets ◽

◽

Z. Rozanova ◽

Maher Alzein ◽

◽

...

Keyword(s):

Retinal Pigment Epithelium ◽

Macular Edema ◽

Cystoid Macular Edema ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Intravitreal Injections ◽

Laser Coagulation

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Caspase-14 Expression Impairs Retinal Pigment Epithelium Barrier Function: Potential Role in Diabetic Macular Edema

BioMed Research International ◽

10.1155/2014/417986 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 9

Author(s):

Selina Beasley ◽

Mohamed El-Sherbiny ◽

Sylvia Megyerdi ◽

Sally El-Shafey ◽

Karishma Choksi ◽

...

Keyword(s):

Macular Edema ◽

Diabetic Macular Edema ◽

Barrier Function ◽

Potential Role ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Retinal Pigment Epithelial Cells ◽

Impedance Sensing ◽

Normal Glucose ◽

The Impact

We recently showed that caspase-14 is a novel molecule in retina with potential role in accelerated vascular cell death during diabetic retinopathy (DR). Here, we evaluated whether caspase-14 is implicated in retinal pigment epithelial cells (RPE) dysfunction under hyperglycemia. The impact of high glucose (HG, 30 mM D-glucose) on caspase-14 expression in human RPE (ARPE-19) cells was tested, which showed significant increase in caspase-14 expression compared with normal glucose (5 mM D-glucose + 25 mM L-glucose). We also evaluated the impact of modulating caspase-14 expression on RPE cells barrier function, phagocytosis, and activation of other caspases using ARPE-19 cells transfected with caspase-14 plasmid or caspase-14 siRNA. We used FITC-dextran flux assay and electric cell substrate impedance sensing (ECIS) to test the changes in RPE cell barrier function. Similar to HG, caspase-14 expression in ARPE-19 cells increased FITC-dextran leakage through the confluent monolayer and decreased the transcellular electrical resistance (TER). These effects of HG were prevented by caspase-14 knockdown. Furthermore, caspase-14 knockdown prevented the HG-induced activation of caspase-1 and caspase-9, the only activated caspases by HG. Phagocytic activity was unaffected by caspase-14 expression. Our results suggest that caspase-14 contributes to RPE cell barrier disruption under hyperglycemic conditions and thus plays a role in the development of diabetic macular edema.

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