AMD (age-related macular degeneration) is a neurodegenerative disease causing irreversible central blindness in the elderly. Apoptosis and inflammation play important roles in AMD pathogenesis. PEDF (pigment epithelium-derived factor) is a potent neurotrophic and anti-inflammatory glycoprotein that protects the retinal neurons and photoreceptors against cell death caused by pathological insults. We studied the effects of PEDF on focal retinal lesions in DKO rd8 (Ccl2(-/-)/Cx3cr1(-/-) on C57BL/6N [Crb1(rd8)]) mice, a model for progressive, focal rd (retinal degeneration). First, we found a significant decrease in PEDF transcript expression in DKO rd8 mouse retina and RPE (retinal pigment epithelium) than WT (wild-type, C57BL/6N). Next, cultured DKO rd8 RPE cells secreted lower levels of PEDF protein in the media than WT. Then the right eyes of DKO rd8 mice were injected intravitreously with recombinant human PEDF protein (1 μg), followed by a subconjunctival injection of PEDF (3 μg) 4 weeks later. The untreated left eyes served as controls. The effect of PEDF was assessed by fundoscopy, ocular histopathology and A2E {[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetra-enyl]-1-(2-hydroxyethyl)-4-[4-methyl-6(2,6,6-trimethyl-1-cyclohexen-1-yl) 1E,3E,5E,7E-hexatrienyl]-pyridinium} levels, as well as apoptotic and inflammatory molecules. The PEDF-treated eyes showed slower progression or attenuation of the focal retinal lesions, fewer and/or smaller photoreceptor and RPE degeneration, and significantly lower A2E, relative to the untreated eyes. In addition, lower expression of apoptotic and inflammatory molecules were detected in the PEDF-treated than untreated eyes. Our results establish that PEDF potently stabilizes photoreceptor degeneration via suppression of both apoptotic and inflammatory pathways. The multiple beneficial effects of PEDF represent a novel approach for potential AMD treatment.
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http://dx.doi.org/10.1042/AN20130028 | DOI Listing |
Ocul Immunol Inflamm
December 2024
Uvea Services, Sankara Nethralaya, Chennai, India.
Purpose: To report a case of exudative retinal detachment (ERD) in a child with Acute retinal necrosis (ARN).
Method: Retrospective Chart Review.
Result: A six-year-old boy presented with anterior uveitis with hypopyon and exudative retinal detachment with peripheral confluent patches of retinitis in the left eye.
Acta Neuropathol Commun
December 2024
Laboratory of Neuropathology, Department of Imaging and Pathology, Leuven Brain Institute, KU Leuven, Leuven, Belgium.
The accumulation of abnormal phosphorylated Tau protein (pTau) in neurons of the brain is a pathological hallmark of Alzheimer's disease (AD). PTau pathology also occurs in the retina of AD cases. Accordingly, questions arise whether retinal pTau can act as a potential seed for inducing cerebral pTau pathology and whether retinal pTau pathology causes degeneration of retinal neurons.
View Article and Find Full Text PDFJ Neural Eng
December 2024
Stanford University, 452 Lomita Mall, Stanford, California, 94305, UNITED STATES.
Objective: Neural interfaces are designed to evoke specific patterns of electrical activity in populations of neurons by stimulating with many electrodes. However, currents passed simultaneously through multiple electrodes often combine nonlinearly to drive neural responses, making evoked responses difficult to predict and control. This response nonlinearity could arise from the interaction of many excitable sites in each cell, any of which can produce a spike.
View Article and Find Full Text PDFEye (Lond)
December 2024
IRCCS Ospedale Policlinico San Martino, Eye Unit, Genova, Italy.
The aim of this article is to comprehensively review the multimodal imaging (MMI) features that define perifoveal vascular anomalous complex (PVAC) and to update the optimal treatment strategies for this disorder with a focus also on the underlying pathogenetic mechanisms. This systematic review was performed based on a search of the PubMed and Embase databases of relevant papers on the subject of PVAC. PVAC is characterized by well-defined MMI findings, including remarkable morphological features with optical coherence tomography (OCT) and OCT angiography (OCTA).
View Article and Find Full Text PDFInt J Retina Vitreous
December 2024
Department of Biomedicine - Unit of Anatomy, Faculty of Medicine, University of Porto, Porto, Portugal.
Purpose: To assess the retinal microvasculature of Systemic Lupus Erythematosus (SLE) patients using Optical Coherence Tomography Angiography (OCTA).
Methods: Twenty adult SLE patients without disease activity and no ocular manifestations were recruited and cross-sectionally assessed. A demographically similar cohort of healthy subjects was used for comparison.
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