A5101798837- Retinal Diseases and Treatments
- Retinal Development and Disorders
- Glaucoma and retinal disorders
- Neuroscience and Neuropharmacology Research
- Retinal and Optic Conditions
- Angiogenesis and VEGF in Cancer
- Corneal surgery and disorders
- Lipid metabolism and disorders
- Complement system in diseases
- Ocular Diseases and Behçet’s Syndrome
- Systemic Lupus Erythematosus Research
- Cellular transport and secretion
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
- Peroxisome Proliferator-Activated Receptors
- Herpesvirus Infections and Treatments
- Virus-based gene therapy research
- Blood Coagulation and Thrombosis Mechanisms
- Retinopathy of Prematurity Studies
- Retinal Imaging and Analysis
- Photochromic and Fluorescence Chemistry
- Receptor Mechanisms and Signaling
- Connexins and lens biology
- Retinal and Macular Surgery
Regeneron (United States)
2016-2023
Azienda Ospedaliera Pugliese Ciaccio
2021
Azienda Ospedaliero Universitaria Ospedali Riuniti
2013
Alcon (United States)
2009-2012
Washington University in St. Louis
1996-2005
Food Research Institute
2001
Stony Brook University
1996
State University of New York
1996
University of California, Irvine
1995
University of Genoa
1992
The conventional outflow pathway is a complex tissue responsible for maintaining intraocular pressure (IOP) homeostasis. coordinated effort of multiple cells with differing responsibilities ensures healthy function and IOP maintenance. Dysfunction one or more resident cell types results in ocular hypertension risk glaucoma, leading cause blindness. In this study, single-cell RNA sequencing was performed to generate comprehensive atlas human tissues. We obtained expression profiles 17,757...
The activity and survival of retinal photoreceptors depend on support functions performed by the pigment epithelium (RPE) oxygen nutrients delivered blood vessels in underlying choroid. By combining single-cell bulk RNA sequencing, we categorized mouse RPE/choroid cell types characterized tissue-specific transcriptomic features choroidal endothelial cells. We found that endothelium adjacent to RPE expresses high levels Indian Hedgehog identified its downstream target as stromal GLI1+...
Glutamate has an important neuromodulatory role in synaptic transmission through metabotropic glutamate receptors (mGluRs) linked to a variety of G-protein-coupled second messenger pathways. Activation these on relay cells the lateral geniculate nucleus (LGN) with agonist trans-(1S,3R)-1-amino-1, 3-cyclopentanedicarboxylic acid produces membrane depolarization that inactivates low-threshold Ca2+ spike, causing transition from burst tonic response mode. The excitatory effects receptor...
CNS function depends on a capacity for plasticity during development, following injury, and in response to changing environmental conditions. Functional alterations signal transduction pathways neurotransmitter receptor expression are possible mechanisms the of such plasticity. In present report, we demonstrate that exposure astrocytes specific growth factors alters both functional activity protein levels glutamate receptor. Exposure basic fibroblast factor, epidermal or transforming...
Nuclear Ca2+ plays a critical role in many cellular functions although its mode (s) of regulation is unclear. This study shows that the metabotropic glutamate receptor, mGlu5, mobilizes nuclear independent cytosolic regulation. Immunocytochemical, ultrastructural, and subcellular fractionation techniques revealed can be localized to membranes heterologous cells as well midbrain cortical neurons. mGlu5 receptors derived from HEK or cell types bound [3H]quisqualate. When loaded with Oregon...
Abstract Bulk RNA sequencing of a tissue captures the gene expression profile from all cell types combined. Single-cell identifies discrete cell-signatures based on transcriptomic identities. Six adult human corneas were processed for single-cell RNAseq and 16 clusters bioinformatically identified. Based their signatures RNAscope results using representative cluster marker genes cornea cross-sections, these confirmed to be stromal keratocytes, endothelium, several subtypes corneal...
Some, perhaps all, G protein-coupled receptors form homo- or heterodimers. We have shown that metabotropic glutamate are covalent dimers, held together by one more disulfide bonds near the N terminus. Here we report how mutating cysteines in this region affect dimerization and function. Covalent is preserved when 57, 93, 99 mutated but lost with replacement at 129. Coimmunoprecipitation under nondenaturing conditions indicates C[129]S mutant receptor remains a dimer, via noncovalent...
Purpose.: Increasing evidence supports a role for complement in the pathogenesis of age-related macular degeneration (AMD). This study evaluated retinal microglia, T-lymphocytes, and deposition light-induced retinopathy model. The effect serotonin (5-hydroxytryptamine, 5-HT1A) agonist on these processes was investigated. Methods.: Rats were dark adapted 24 hours before 6-hour blue light exposure. Some animals predosed subcutaneously with AL-8309A. Retinas at different times after Paraffin...
Complement is a key component of the innate immune system. Inappropriate complement activation underlies pathophysiology variety diseases. 5 (C5) validated therapeutic target for complement-mediated diseases, but development new therapeutics has been limited by paucity preclinical models to evaluate pharmacokinetic (PK) and pharmacodynamic (PD) properties candidate therapies. The present report describes novel humanized C5 mouse its utility in evaluating panel fully human anti-C5 antibodies....
Anti-vascular endothelial growth factor (VEGF) therapies have improved clinical outcomes for patients with cancers and retinal vascular diseases. Three anti-VEGF agents, pegaptanib, ranibizumab, aflibercept, are approved ophthalmic indications, while bevacizumab is to treat colorectal, lung, renal cancers, but also used off-label ocular The efficacy of relative ranibizumab in treating neovascular age-related macular degeneration has been assessed several trials. However, questions persist...
Purpose: Birdshot chorioretinopathy (BSCR) is strongly associated with HLA-A29. This study was designed to elucidate the genetic modifiers of BSCR in HLA-A29 carriers. Methods: We sequenced largest cohort date, including 286 cases and 108 HLA-A29–positive controls determine genome-wide common rare variant associations. further typed HLA alleles 45,386 European ancestry identify that associate risk. Results: Carrying a second allele belongs HLA-Aw19 broad antigen family (including HLA-A29,...
Abstract X-linked juvenile retinoschisis (XLRS) is an early-onset inherited condition that affects primarily males and characterized by cystic lesions of the inner retina, decreased visual acuity contrast sensitivity a selective reduction electroretinogram (ERG) b-wave. Although XLRS genetically heterogeneous, all mouse models developed to date involve engineered or spontaneous null mutations. In present study, we have studied three new Rs1 mutant models: (1) knockout with inserted lacZ...
Abstract Angiogenesis is largely driven by motile endothelial tip-cells capable of invading avascular tissue domains and enabling new vessel formation. Highly responsive to Vascular Endothelial Growth-Factor-A (VEGFA), also suppress angiogenic sprouting in adjacent stalk cells, thus have been a primary therapeutic focus addressing neovascular pathologies. Surprisingly, however, there remains paucity specific tip-cell markers. Here, we employ transcriptional profiling lacZ reporter allele...
Abstract: Thrombin is one of the first regulatory molecules present at sites CNS trauma or injury. Exposure neuronal and glial cells to thrombin produces potent morphological as well cytoprotective cytotoxic effects, but little known about how this important modulator affects neurotransmitter signaling. In astrocyte cultures that have been morphologically differentiated by exposure transforming growth factor‐α, addition induced a retraction astrocytic processes suppressed stimulation...
BackgroundCarboxyethylpyrrole (CEP) adducts are oxidative modifications derived from docosahexaenoate-containing lipids that elevated in ocular tissues and plasma age-related macular degeneration (AMD) rodents exposed to intense light. The goal of this study was determine whether light-induced CEP autoantibodies modulated by pretreatment with AL-8309A under conditions prevent photo-oxidative damage rat retina. is a serotonin 5-HT1A receptor agonist. MethodsAlbino rats were dark adapted prior...
We establish and characterize the chronic retinal neovascularization (RNV) induced by intravitreal (IVT) injection of DL-α-aminoadipic acid (AAA) in a rabbit model investigate extent duration inhibitory actions IVT aflibercept on RNV.Rabbits received single AAA, with weekly follow-up fundus photography, fluorescein angiography (FA), optical coherence tomography (OCT). After 10 weeks, they or control injection. RNV leakage was quantified from FA image analysis Photoshop. Some eyes were...
Despite years of effort, sustained delivery protein therapeutics remains an unmet need due to three primary challenges - dose, duration, and stability. The work presented here provides a design methodology for polycaprolactone reservoir-based thin film devices suitable long-acting the back eye. First, challenge formulating highly concentrated in device reservoir was addressed by improving stability with solubility-reducing excipients. Next, predictive correlations between parameters...