- Factors Associated With Retinal Vessel Diameters in an Elderly Population: the Thessaloniki Eye Study. [Journal Article]
- IOInvest Ophthalmol Vis Sci 2019 May 01; 60(6):2208-2217
- CONCLUSIONS: Our study confirms previous reports about the association of age and BP with vessel diameters. The negative correlation between BP and CRAE seems to be guided by the effect of diastolic BP as higher systolic BP is independently associated with higher values of CRAE. The association of BP status with retinal vessel diameters is determined by diastolic BP status in our population. Multiple other factors are also independently associated with retinal vessel diameters.
- New players in phototherapy: photopharmacology and bio-integrated optoelectronics. [Review]
- COCurr Opin Chem Biol 2019 May 17; 50:145-151
- Photodynamic therapy and phototherapy are used in the clinic to treat dermatological conditions, cancer, macular degeneration, and a variety of other diseases. Despite their long history and widespre…
Photodynamic therapy and phototherapy are used in the clinic to treat dermatological conditions, cancer, macular degeneration, and a variety of other diseases. Despite their long history and widespread application, the scope of these therapeutic approaches has been limited by a lack of specificity and challenges with light delivery. In recent years, much progress has been made in these regards. Photopharmacology has provided drug-like molecules that change their efficacy upon irradiation and allow for the optical control of a wide range of defined biological targets. Many photopharmaceuticals are now used in vivo and some show promising results in preclinical development. At the same time, new bioelectronics for subdermal light delivery have been engineered that could enable phototherapy deep in tissue, for example within the human brain. These developments could increase the impact of photodynamic therapy in human precision medicine.
- Vascular protection of salicin on IL-1β-induced endothelial inflammatory response and damages in retinal endothelial cells. [Journal Article]
- ACArtif Cells Nanomed Biotechnol 2019; 47(1):1995-2002
- Retinal endothelial cells (RECs) are involved in many ocular diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. Salicin is the major ingredient of willow bark extract, …
Retinal endothelial cells (RECs) are involved in many ocular diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. Salicin is the major ingredient of willow bark extract, and it has been shown to be a potent anti-inflammatory agent. We aim to explore whether salicin has a vascular protective effect in RECs. Our data indicate that the presence of salicin in RECs culture media ameliorates interleukin-1β (IL-1β)-induced cellular reactive oxygen species (ROS) production and NADPH oxidase 4 (NOX-4) expression. At the cellular level, salicin attenuates IL-1β-induced mitochondrial injury as revealed by its preservation on mitochondrial membrane potential (MMP). Furthermore, salicin inhibits IL-1β-induced production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1), vascular adhesion molecules such as intercellular cell adhesion molecule-1 (iCAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and high-mobility group protein 1 (HMGB-1). On the other hand, salicin recovers IL-1β-induced reduction of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) release. The presence of salicin significantly reduces the IL-1β-induced release of lactate dehydrogenase (LDH), indicating that it mitigates cytokine caused cytotoxicity. Mechanistically, we show that salicin suppresses IL-1β-induced activation of the nuclear factor-kappa B (NF-κB) signaling as revealed by its suppression on nuclear p65 protein and transfected NF-κB promoter. Collectively, our study demonstrates by multiple facets of its mechanisms that salicin is a protective agent in retinal endothelial cells. These results imply its potential use in therapeutic usage of retinal disease.
- Understanding Visual Impairment and Its Impact on Patients: A Simulation-Based Training in Undergraduate Medical Education. [Journal Article]
- JMJ Med Educ Curric Dev 2019 Jan-Dec; 6:2382120519843854
- CONCLUSIONS: Simulation activities are valuable additions to the undergraduate curriculum. Such activities can potentially enable greater empathy for our visually impaired patients.
- Characterization of a functionally active primary microglial cell culture from the pig retina. [Journal Article]
- EEExp Eye Res 2019 May 16
- Retinal inflammation is an integral component of many retinal diseases including diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinopathy of prematurity (ROP). Inflammation i…
Retinal inflammation is an integral component of many retinal diseases including diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinopathy of prematurity (ROP). Inflammation is commonly initiated and perpetuated by myeloid-derived immune cells. In the retina, microglial cells are resident macrophages with myeloid origins, which acts as the first responders involved in the innate immune system. To understand the disease pathogenesis, the use of isolated retinal cell culture model is vital for the examination of multiple cellular responses to injury or trauma. The pig retina resembles human retina in terms of tissue architecture, vasculature, and topography. Additionally, it is a better model than the rodent retina because of the presence of the pseudomacula. In the present study, we sought to establish and characterize pig retinal primary microglial cell (pMicroglia) culture. We used pig eyes from the local abattoir and optimized pMicroglia cultures using multiple cell culture conditions and methods. The best results were obtained by seeding cells in DMEM-high glucose media for 18 days followed by shaking of the culture plate. The resulting pMicroglia were characterized by cellular morphology, phenotype, and immunostaining with Iba-1, CD68, P2Y12, CD163, CD14, and Isolectin GS-IB4. Generated pMicroglia were found functionally active in phagocytosis assay and responsive to lipopolysaccharides (LPS) in dose-dependent production of IL-1β. Furthermore, they showed increased secretion of pro-inflammatory cytokines with LPS treatment. Thus, we report a novel and reproducible method for the isolation of primary microglial cells from pig eyes, which may be useful for studying retinal diseases.
- How Successful is Switching from Bevacizumab or Ranibizumab to Aflibercept in Age-Related Macular Degeneration? A Systematic Overview. [Review]
- ATAdv Ther 2019 May 17
- Emerging anti-vascular endothelial growth factor (anti-VEGF) therapies for neovascular age-related macular degeneration (nAMD) have revolutionised medical retina practice and the management and event…
Emerging anti-vascular endothelial growth factor (anti-VEGF) therapies for neovascular age-related macular degeneration (nAMD) have revolutionised medical retina practice and the management and eventual outcome of nAMD. Recent research has focused on evaluating and comparing the efficacy of the two most widely employed anti-VEGF agents, bevacizumab and ranibizumab; however, a subgroup of patients with nAMD demonstrates a suboptimal response to standard therapy. We have therefore conducted a review of pertinent studies published until August 2018 which have documented the clinical efficacy when switching to a different anti-VEGF. Evidence on baseline disease characteristics, injection frequency and disease outcome has been obtained for patients treated with ranibizumab 0.5 mg and/or bevacizumab 1.25 mg and were switched to aflibercept 2 mg. Our review identified 45 studies investigating switching to aflibercept. Our review showed a clear anatomical benefit after the switch in terms of central retinal thickness and pigment epithelium detachment characteristics, whereas the functional outcomes were variable. Remarkable heterogeneity was documented among the relevant studies with regard to several factors including the baseline characteristics of the cohorts, the non-response definition and previous treatment protocols. Larger prospective trials with appropriate control arms are therefore required to elucidate the potential benefit when switching between anti-VEGF agents in refractory nAMD.
- Loss of PGC-1α in RPE induces mesenchymal transition and promotes retinal degeneration. [Journal Article]
- LSLife Sci Alliance 2019; 2(3)
- The retinal pigment epithelium (RPE) supports visual processing and photoreceptor homeostasis via energetically demanding cellular functions. Here, we describe the consequences of repressing peroxiso…
The retinal pigment epithelium (RPE) supports visual processing and photoreceptor homeostasis via energetically demanding cellular functions. Here, we describe the consequences of repressing peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α), a master regulator of mitochondrial function and biogenesis, on RPE epithelial integrity. The sustained silencing of PGC-1α in differentiating human RPE cells affected mitochondria/autophagy function, redox state, and impaired energy sensor activity ultimately inducing epithelial to mesenchymal transition (EMT). Adult conditional knockout of PGC-1 coactivators in mice resulted in rapid RPE dysfunction and transdifferentiation associated with severe photoreceptor degeneration. RPE anomalies were characteristic of autophagic defect and mesenchymal transition comparable with the ones observed in age-related macular degeneration. These findings demonstrate that PGC-1α is required to maintain the functional and phenotypic status of RPE by supporting the cells' oxidative metabolism and autophagy-mediated repression of EMT.
- Use of Bevacizumab and Ranibizumab for Wet Age-Related Macular Degeneration: Influence of CATT Results and Introduction of Aflibercept. [Journal Article]
- AJAm J Ophthalmol 2019 May 14
- CONCLUSIONS: Many ophthalmologists who favored ranibizumab switched to bevacizumab after CATT publication while most who favored bevacizumab prior to CATT publication continued favoring it afterwards. Aflibercept's introduction had little impact on preferences for ranibizumab or bevacizumab.
- Classification of Strokes in Patients Receiving Intravitreal Anti-Vascular Endothelial Growth Factor. [Journal Article]
- OSOphthalmic Surg Lasers Imaging Retina 2019 May 01; 50(5):e140-e157
- CONCLUSIONS: The authors' data suggest there is no predilection to the development of ischemic infarcts or hemorrhagic strokes in those patients receiving intravitreal anti-VEGF compared with control populations. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e140-e157.].
New Search Next
- A lasered mouse model of retinal degeneration displays progressive outer retinal pathology providing insights into early geographic atrophy. [Journal Article]
- SRSci Rep 2019 May 16; 9(1):7475
- Early stages of geographic atrophy (GA) age-related macular degeneration is characterised by the demise of photoreceptors, which precedes the loss of underlying retinal pigment epithelial (RPE) cells…
Early stages of geographic atrophy (GA) age-related macular degeneration is characterised by the demise of photoreceptors, which precedes the loss of underlying retinal pigment epithelial (RPE) cells. Sight-loss due to GA has no effective treatment; reflecting both the complexity of the disease and the lack of suitable animal models for testing potential therapies. We report the development and characterisation of a laser-induced mouse model with early GA-like pathology. Retinas were lasered at adjacent sites using a 810 nm laser (1.9 J/spot), resulting in the development of confluent, hypopigmented central lesions with well-defined borders. Optical Coherence Tomography over 2-months showed progressive obliteration of photoreceptors with hyper-reflective outer plexiform and RPE/Bruch's membrane (BrM) layers within lesions, but an unaffected inner retina. Light/electron microscopy after 3-months revealed lesions without photoreceptors, leaving the outer plexiform layer apposed to the RPE. We observed outer segment debris, hypo/hyperpigmented RPE, abnormal apical-basal RPE surfaces and BrM thickening. Lesions had wedge-shaped margins, extended zones of damage, activated Müller cells, microglial recruitment and functional retinal deficits. mRNA studies showed complement and inflammasome activation, microglial/macrophage phagocytosis and oxidative stress providing mechanistic insights into GA. We propose this mouse model as an attractive tool for early GA studies and drug-discovery.