- Retinal pigment epithelium hyperplasia overlying pigment epithelial detachment in age-related macular degeneration can masquerade as neovascularization on optical coherence tomography angiography. [Journal Article]
- GAGraefes Arch Clin Exp Ophthalmol 2018 Sep 18
- CONCLUSIONS: RPE hyperplasia overlying PED in AMD can masquerade as neovascularization on OCTA. To avoid misdiagnosis and unnecessary treatment, this RPE hyperplasia-related image artifact should be considered when interpreting OCTA images.
- The small GTPase Rab28 is required for phagocytosis of cone outer segments by the murine retinal pigmented epithelium. [Journal Article]
- JBJ Biol Chem 2018 Sep 18
- Rab28, a member of the RAS oncogene family is a ubiquitous, farnesylated, small GTPase of unknown function present in photoreceptors and the retinal pigmented epithelium (RPE). Nonsense mutations of ...
Rab28, a member of the RAS oncogene family is a ubiquitous, farnesylated, small GTPase of unknown function present in photoreceptors and the retinal pigmented epithelium (RPE). Nonsense mutations of the human RAB28 gene cause recessive cone-rod dystrophy 18 (CRD18), characterized by macular hyperpigmentation, progressive loss of visual acuity, RPE atrophy and severely attenuated cone and rod electroretinography (ERG) responses. In an attempt to elucidate the disease-causing mechanism, we generated Rab28-/- mice by deleting exon 3 and truncating Rab28 after exon 2. We found that Rab28-/- mice recapitulate features of the human dystrophy, i.e., they exhibited reduced cone and rod ERG responses and progressive retina degeneration. Cones of Rab28-/- mice extended their outer segments (OSs) to the RPE apical processes and formed enlarged, balloon-like distal tips before undergoing degeneration. The visual pigment content of WT and Rab28-/- cones was comparable before the onset of degeneration. Cone phagosomes were almost absent in Rab28-/- mice, whereas rod phagosomes displayed normal levels. A protein-protein interaction screen identified several Rab28-interacting proteins, including the prenyl-binding protein phosphodiesterase 6 δ-subunit (PDE6D) and a voltage-gated potassium channel subfamily J member 13 (KCNJ13) present in the RPE apical processes. Of note, loss of PDE6D prevented delivery of Rab28 to OSs. Taken together, these findings reveal that Rab28 is required for shedding and phagocytosis of cone OS discs.
- Complement System and Age-Related Macular Degeneration: Implications of Gene-Environment Interaction for Preventive and Personalized Medicine. [Review]
- BRBiomed Res Int 2018; 2018:7532507
- Age-related macular degeneration (AMD) is the most common cause of visual loss in developed countries, with a significant economic and social burden on public health. Although genome-wide and gene-ca...
Age-related macular degeneration (AMD) is the most common cause of visual loss in developed countries, with a significant economic and social burden on public health. Although genome-wide and gene-candidate studies have been enabled to identify genetic variants in the complement system associated with AMD pathogenesis, the effect of gene-environment interaction is still under debate. In this review we provide an overview of the role of complement system and its genetic variants in AMD, summarizing the consequences of the interaction between genetic and environmental risk factors on AMD onset, progression, and therapeutic response. Finally, we discuss the perspectives of current evidence in the field of genomics driven personalized medicine and public health.
- Application of artificial intelligence in ophthalmology. [Review]
- IJInt J Ophthalmol 2018; 11(9):1555-1561
- Artificial intelligence is a general term that means to accomplish a task mainly by a computer, with the least human beings participation, and it is widely accepted as the invention of robots. With t...
Artificial intelligence is a general term that means to accomplish a task mainly by a computer, with the least human beings participation, and it is widely accepted as the invention of robots. With the development of this new technology, artificial intelligence has been one of the most influential information technology revolutions. We searched these English-language studies relative to ophthalmology published on PubMed and Springer databases. The application of artificial intelligence in ophthalmology mainly concentrates on the diseases with a high incidence, such as diabetic retinopathy, age-related macular degeneration, glaucoma, retinopathy of prematurity, age-related or congenital cataract and few with retinal vein occlusion. According to the above studies, we conclude that the sensitivity of detection and accuracy for proliferative diabetic retinopathy ranged from 75% to 91.7%, for non-proliferative diabetic retinopathy ranged from 75% to 94.7%, for age-related macular degeneration it ranged from 75% to 100%, for retinopathy of prematurity ranged over 95%, for retinal vein occlusion just one study reported ranged over 97%, for glaucoma ranged 63.7% to 93.1%, and for cataract it achieved a more than 70% similarity against clinical grading.
- Modulation of three key innate immune pathways for the most common retinal degenerative diseases. [Review]
- EMEMBO Mol Med 2018 Sep 17
- This review highlights the role of three key immune pathways in the pathophysiology of major retinal degenerative diseases including diabetic retinopathy, age-related macular degeneration, and rare r...
This review highlights the role of three key immune pathways in the pathophysiology of major retinal degenerative diseases including diabetic retinopathy, age-related macular degeneration, and rare retinal dystrophies. We first discuss the mechanisms how loss of retinal homeostasis evokes an unbalanced retinal immune reaction involving responses of local microglia and recruited macrophages, activity of the alternative complement system, and inflammasome assembly in the retinal pigment epithelium. Presenting these key mechanisms as complementary targets, we specifically emphasize the concept of immunomodulation as potential treatment strategy to prevent or delay vision loss. Promising molecules are ligands for phagocyte receptors, specific inhibitors of complement activation products, and inflammasome inhibitors. We comprehensively summarize the scientific evidence for this strategy from preclinical animal models, human ocular tissue analyses, and clinical trials evolving in the last few years.
- A review of the multifunctionality of angiopoietin-like 4 in eye disease. [Journal Article]
- BRBiosci Rep 2018 Sep 17
- Angiopoietin-like protein 4 is a multifunctional cytokine regulating vascular permeability, angiogenesis, and inflammation. Dysregulations on these responses contribute to the pathogenesis of ischemi...
Angiopoietin-like protein 4 is a multifunctional cytokine regulating vascular permeability, angiogenesis, and inflammation. Dysregulations on these responses contribute to the pathogenesis of ischemic retinopathies such as diabetic retinopathy, age-related macular degeneration, retinal vein occlusion and sickle cell retinopathy. However, the role of ANGPTL4 in these diseases remains controversial. Here, we summarize the functional mechanisms of ANGPTL4 in several diseases. We highlight original studies that provide detailed data about the mechanisms of action for ANGPTL4, its applications as a diagnostic or prognostic biomarker, and its use as a potential therapeutic target. Taken together, the discussions in this review will help us gain a better understanding of the molecular mechanisms by which ANGPTL4 functions in eye disease and will provide directions for future research.
- Repeatability of Split-Spectrum Amplitude-Decorrelation Angiography to Assess Capillary Perfusion Density Within Optical Coherence Tomography. [Journal Article]
- OSOphthalmic Surg Lasers Imaging Retina 2018 Sep 01; 49(9):e9-e19
- CONCLUSIONS: The SSADA OCT angiography analysis has a low level of variability between measurements and, thus, is a reliable tool for evaluation of retinal perfusion. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e9-e19.].
- Suspended Scattering Particles in Motion: A Novel Feature of OCT Angiography in Exudative Maculopathies. [Journal Article]
- OROphthalmol Retina 2018; 2(7):694-702
- CONCLUSIONS: Clinical data suggest that SSPiM is a novel imaging feature of retinal vascular diseases that was not appreciated prior to the use of OCTA. We characterized several novel features of SSPiM and demonstrated that at least in some cases it resolves with residual hard exudate.
- Effect of Phacoemulsification on Visual Acuity and Macular Morphology in Patients with Wet Age-Related Macular Degeneration. [Journal Article]
- MSMed Sci Monit 2018 Sep 17; 24:6517-6524
- CONCLUSIONS: Phacoemulsification performed in eyes with wet age-related macular degeneration during the inactive phase of the disease significantly improves visual acuity. In addition, it does not significantly influence the frequency of intravitreal injections of anti-vascular endothelial growth factor agents or disease activity.
New Search Next
- Inhibition of Atypical Protein Kinase C Reduces Inflammation-Induced Retinal Vascular Permeability. [Journal Article]
- AJAm J Pathol 2018 Sep 12
- Changes in permeability of retinal blood vessels contribute to macular edema and the pathophysiology of numerous ocular diseases, including diabetic retinopathy, retinal vein occlusions, and macular ...
Changes in permeability of retinal blood vessels contribute to macular edema and the pathophysiology of numerous ocular diseases, including diabetic retinopathy, retinal vein occlusions, and macular degeneration. Vascular endothelial growth factor (VEGF) induces retinal permeability and macular thickening in these diseases. However, inflammatory agents, such as tumor necrosis factor-α (TNF-α), also may drive vascular permeability, specifically in patients unresponsive to anti-VEGF therapy. Recent evidence suggests VEGF and TNF-α induce permeability through distinct mechanisms; however, both require the activation of atypical protein kinase C (aPKC). We provide evidence, using genetic mouse models and therapeutic intervention with small molecules, that inhibition of aPKC prevented or reduced vascular permeability in animal models of retinal inflammation. Expression of a kinase-dead aPKC transgene, driven by a vascular and hematopoietic restricted promoter, reduced retinal vascular permeability in an ischemia-reperfusion model of retinal injury. This effect was recapitulated with a small-molecule inhibitor of aPKC. Expression of the kinase-dead aPKC transgene dramatically reduced the expression of inflammatory factors and blocked the attraction of inflammatory monocytes and granulocytes after ischemic injury. Coinjection of VEGF with TNF-α was sufficient to induce permeability, edema, and retinal inflammation, and treatment with an aPKC inhibitor prevented VEGF/TNF-α-induced permeability. These data suggest that aPKC contributes to inflammation-driven retinal vascular pathology and may be an attractive target for therapeutic intervention.