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Joshua Dunaief

Ebenezer Daniel, Gui-Shuang Ying, Benjamin J Kim, Cynthia A Toth, Frederick Ferris, Daniel F Martin, Juan E Grunwald, Glenn J Jaffe, Joshua L Dunaief, Wei Pan, Maureen G Maguire
OBJECTIVE: To describe changes in visual acuity (VA) and macular morphology at 5 years in eyes with non-fibrotic scars (NFS) identified at 1 year in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). DESIGN: Prospective cohort study within a randomized clinical trial. PARTICIPANTS: Participants in CATT. METHODS: Participants assigned to ranibizumab or bevacizumab and to 1 of 3 dosing regimens were released from the clinical trial protocol after 2 years and recalled at 5 years...
November 23, 2018: Ophthalmology
Wanting Shu, Joshua L Dunaief
Iron is essential for life, while excess iron can be toxic. Iron generates hydroxyl radical, which is the most reactive free radical, causing oxidative stress. Since iron is absorbed through the diet but not excreted from the body, it accumulates with age in tissues, including the retina, consequently leading to age-related toxicity. This accumulation is further promoted by inflammation. Hereditary diseases such as aceruloplasminemia, Friedreich's ataxia, pantothenate kinase-associated neurodegeneration, and posterior column ataxia with retinitis pigmentosa involve retinal degeneration associated with iron dysregulation...
October 22, 2018: Pharmaceuticals
S Amal Hussnain, Rosa Dolz-Marco, Joshua L Dunaief, Christine A Curcio, K Bailey Freund
PURPOSE: To describe patterns of hypoautofluorescence in eyes with neovascular age-related macular degeneration occurring after subretinal hemorrhage. METHODS: This was a retrospective descriptive analysis of neovascular age-related macular degeneration eyes presenting with subretinal hemorrhage over the last 5 years that underwent serial multimodal imaging. A review of color fundus photographs, fundus autofluorescence, near-infrared reflectance, and optical coherence tomography was performed at baseline and all available follow-up visits to document the course and evolution of subretinal hemorrhage in these eyes...
October 22, 2018: Retina
Aicha Saadane, Alexey Petrov, Natalia Mast, Nicole El-Darzi, Tung Dao, Ahab Alnemri, Ying Song, Joshua L Dunaief, Irina A Pikuleva
Apolipoprotein E (APOE) is a component of lipid-transporting particles and a recognition ligand for receptors, which bind these particles. The APOE isoform 2 is a risk factor for age-related macular degeneration; nevertheless APOE absence in humans and mice does not significantly affect the retina. We found that retinal cholesterol biosynthesis and the levels of retinal cholesterol were increased in Apoe-/- mice, whereas cholesterol elimination by metabolism was decreased. No focal cholesterol deposits were observed in the Apoe-/- retina...
October 17, 2018: Journal of Lipid Research
Brie K Fuqua, Yan Lu, David M Frazer, Deepak Darshan, Sarah J Wilkins, Linda Dunn, Alex V Loguinov, Scott C Kogan, Pavle Matak, Huijun Chen, Joshua L Dunaief, Chris D Vulpe, Gregory J Anderson
Background & Aims: Multicopper ferroxidases (MCFs) facilitate intestinal iron absorption and systemic iron recycling, likely by a mechanism involving the oxidization of Fe2+ from the iron exporter ferroportin 1 for delivery to the circulating Fe3+ carrier transferrin. Hephaestin (HEPH), the only MCF known to be expressed in enterocytes, aids in the basolateral transfer of dietary iron to the blood. Mice lacking HEPH in the whole body ( Heph -/- ) or intestine alone ( Heph int/int ) exhibit defects in dietary iron absorption but still survive and grow...
2018: Cellular and Molecular Gastroenterology and Hepatology
Delu Song, Imran Mohammed, Rupak Bhuyan, Takashi Miwa, Allison Lesher Williams, Damodar Gullipalli, Sayaka Sato, Ying Song, Joshua L Dunaief, Wen-Chao Song
Purpose: Dense deposit disease (DDD) is caused by dysregulation of the alternative pathway of the complement cascade and characterized by electron-dense deposits in the kidney glomerular basement membrane (GBM) and drusen in Bruch's membrane (BrM). Complement factor H (fH) and factor properdin (fP) regulate complement activation; fH inhibits alternative pathway (AP) activation, whereas fP promotes it. We report pathologic changes in eyes of an fH and fP double-mutant mouse, which we previously showed have dense deposits in the GBM and early mortality from nephropathy...
July 2, 2018: Investigative Ophthalmology & Visual Science
Keiko Ueda, Hye Jin Kim, Jin Zhao, Ying Song, Joshua L Dunaief, Janet R Sparrow
Intracellular Fe plays a key role in redox active energy and electron transfer. We sought to understand how Fe levels impact the retina, given that retinal pigment epithelial (RPE) cells are also challenged by accumulations of vitamin A aldehyde adducts (bisretinoid lipofuscin) that photogenerate reactive oxygen species and photodecompose into damaging aldehyde- and dicarbonyl-bearing species. In mice treated with the Fe chelator deferiprone (DFP), intracellular Fe levels, as reflected in transferrin receptor mRNA expression, were reduced...
May 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jiashuo Zheng, Ruiwei Jiang, Min Chen, Zaitunamu Maimaitiming, Junzhuo Wang, Gregory J Anderson, Chris D Vulpe, Joshua L Dunaief, Huijun Chen
Background: The accumulation of iron occurs in the central nervous system (CNS) in several neurodegenerative diseases. Although multi-copper ferroxidases (MCFs) play an important role in cellular iron metabolism and homeostasis, the mechanism of MCFs in the CNS remains unclear. Objective: The aim was to study the role of MCFs in CNS iron metabolism and homeostasis by using hephaestin/ceruloplasmin (Heph/Cp) double knockout (KO) mice. Methods: Heph/Cp double KO male mice were generated by crossing both single KO mice...
April 1, 2018: Journal of Nutrition
Benjamin J Kim, David J Irwin, Delu Song, Ebenezer Daniel, Jennifer D Leveque, Aaishah R Raquib, Wei Pan, Gui-Shuang Ying, Tomas S Aleman, Joshua L Dunaief, Murray Grossman
OBJECTIVE: Whereas Alzheimer disease (AD) is associated with inner retina thinning visualized by spectral-domain optical coherence tomography (SD-OCT), we sought to determine if the retina has a distinguishing biomarker for frontotemporal degeneration (FTD). METHODS: Using a cross-sectional design, we examined retinal structure in 38 consecutively enrolled patients with FTD and 44 controls using a standard SD-OCT protocol. Retinal layers were segmented with the Iowa Reference Algorithm...
October 10, 2017: Neurology
Bailey Baumann, Jacob Sterling, Ying Song, Delu Song, Marcus Fruttiger, Mark Gillies, Weiyong Shen, Joshua L Dunaief
Purpose: Retinal iron accumulation is observed in a wide range of retinal degenerative diseases, including AMD. Previous work suggests that Müller glial cells may be important mediators of retinal iron transport, distribution, and regulation. A transgenic model of Müller cell loss recently demonstrated that primary Müller cell ablation leads to blood-retinal barrier leakage and photoreceptor degeneration, and it recapitulates clinical features observed in macular telangiectasia type 2 (MacTel2), a rare human disease that features Müller cell loss...
August 1, 2017: Investigative Ophthalmology & Visual Science
Shounan Qi, Chenguang Wang, Delu Song, Ying Song, Joshua L Dunaief
PURPOSE: (-)-epigallocatechin-3-gallate (EGCG), a major catechin component of green tea, is reported to delay or prevent certain forms of cancer, arthritis, cardiovascular disease, and neurodegenerative disorders. In this study, we determined if systemically administered EGCG could protect the retina against light damage (LD) in mice. METHODS: BALB/cJ mice were treated with either EGCG or saline via intraperitoneal (IP) injection, and then placed under constant cool white light-emitting diode (LED) light (10,000 lux) for 5 h...
2017: Molecular Vision
Delu Song, Michael E Sulewski, Chenguang Wang, Jiantao Song, Rupak Bhuyan, Jacob Sterling, Esther Clark, Wen-Chao Song, Joshua L Dunaief
PURPOSE: The complement system is involved in the pathogenesis of age-related macular degeneration (AMD). Because activated microglia are also associated with AMD, we studied the relationship between complement anaphylatoxin receptors and microglial recruitment. METHODS: We assessed the effect of anaphylatoxin C3a receptor (C3aR) and C5a receptor (C5aR) knockout (KO) on light damage-induced migration of microglia/macrophages into the mouse outer retina via immunofluorescence and real-time quantitative PCR...
2017: Molecular Vision
Yoshiyasu Ueda, Imran Mohammed, Delu Song, Damodar Gullipalli, Lin Zhou, Sayaka Sato, Yuan Wang, Shuchi Gupta, Zhongjian Cheng, Hong Wang, Jialing Bao, Yingying Mao, Lawrence Brass, X Long Zheng, Takashi Miwa, Matthew Palmer, Joshua Dunaief, Wen-Chao Song
Complement plays a key role in host defense, but its dysregulation can cause autologous tissue injury. Complement activation is normally controlled by regulatory proteins, including factor H (FH) in plasma and membrane cofactor protein (MCP) on the cell surface. Mutations in FH and MCP are linked to atypical hemolytic uremic syndrome, a type of thrombotic microangiopathy (TMA) that causes renal failure. We describe here that disruption of FH function on the cell surface can also lead to disseminated complement-dependent macrovascular thrombosis...
March 2, 2017: Blood
Jacob Sterling, Samyuktha Guttha, Ying Song, Delu Song, Majda Hadziahmetovic, Joshua L Dunaief
Intracellular retinal iron accumulation has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of irreversible blindness among individuals over the age of 50. Ceruloplasmin/hephaestin double knockout mice (Cp/Heph DKO) and hepcidin knockout mice (Hepc KO) accumulate retinal iron and model some features of AMD. Two canonical pathways govern cellular iron import - transferrin-bound iron import and non-transferrin bound iron import. In Cp/Heph DKO and Hepc KO iron-loaded retinas, transferrin-bound iron import is downregulated...
February 2017: Experimental Eye Research
Bo Jiang, Guohao Liu, Jiashuo Zheng, Mengxia Chen, Zaitunamu Maimaitiming, Min Chen, Shunli Liu, Ruiwei Jiang, Brie K Fuqua, Joshua L Dunaief, Chris D Vulpe, Gregory J Anderson, Hongwei Wang, Huijun Chen
Multicopper ferroxidases (MCFs) play an important role in cellular iron homeostasis. However, the role of MCFs in renal metabolism remains unclear. We used Hephaestin (Heph) and Ceruloplasmin (Cp) single or double (Heph/Cp) knockout (KO) mice to study the roles of MCFs in the kidney. Renal iron levels and the expression of iron metabolism genes were examined. The non-heme iron content both in the renal cortex and medulla of Heph/Cp KO mice was significantly increased. Perls' Prussian blue staining showed iron accumulation on the apical side of renal tubular cells in Heph/Cp KO mice...
December 19, 2016: Scientific Reports
Delu Song, Brooks Wilson, Liangliang Zhao, Rupak Bhuyan, Mausumi Bandyopadhyay, Arkady Lyubarsky, Chen Yu, Yafeng Li, Levi Kanu, Takashi Miwa, Wen-Chao Song, Silvia C Finnemann, Bärbel Rohrer, Joshua L Dunaief
Complement dysregulation plays a key role in the pathogenesis of age-related macular degeneration (AMD), but the specific mechanisms are incompletely understood. Complement also potentiates retinal degeneration in the murine light damage model. To test the retinal function of CD59a, a complement inhibitor, CD59a knockout (KO) mice were used for light damage (LD) experiments. Retinal degeneration and function were compared in WT versus KO mice following light damage. Gene expression changes, endoplasmic reticulum (ER) stress, and glial cell activation were also compared...
2016: PloS One
Daniel Sarezky, Aaishah R Raquib, Joshua L Dunaief, Benjamin J Kim
PURPOSE: Alpha lipoic acid (ALA) is an antioxidant and iron-chelating supplement that has potential benefits for geographic atrophy in dry age-related macular degeneration as well as other eye diseases. The purpose of this study was to determine the tolerability of ALA in the elderly population. PATIENTS AND METHODS: Fifteen subjects, age ≥65 years, took sequential ALA doses of 600, 800, and 1,200 mg. Each dose was taken once daily with a meal for 5 days. After each dose was taken by the subjects for 5 days, the subjects were contacted by phone, a review of systems was performed, and they were asked if they thought they could tolerate taking that dose of ALA for an extended period of time...
2016: Clinical Ophthalmology
Delu Song, Levi N Kanu, Yafeng Li, Kristen L Kelly, Rupak K Bhuyan, Tomas Aleman, Jessica I W Morgan, Joshua L Dunaief
Iron accumulation in the retina is associated with the development of age-related macular degeneration (AMD). IV iron is a common method to treat iron deficiency anemia in adults, and its retinal manifestations have not hitherto been identified. To assess whether IV iron formulations can be retina-toxic, we generated a mouse model for iron-induced retinal damage. Male C57BL/6J mice were randomized into groups receiving IV iron-sucrose (+Fe) or 30% sucrose (-Fe). Iron levels in neurosensory retina (NSR), retinal pigment epithelium (RPE), and choroid were assessed using immunofluorescence, quantitative PCR, and the Perls' iron stain...
October 2016: Experimental Eye Research
Joshua L Dunaief
No abstract text is available yet for this article.
May 1, 2016: Investigative Ophthalmology & Visual Science
Milan Theurl, Delu Song, Esther Clark, Jacob Sterling, Steve Grieco, Sandro Altamura, Bruno Galy, Matthias Hentze, Martina U Muckenthaler, Joshua L Dunaief
Because ferroportin (Fpn) is the only known mammalian cellular iron exporter, understanding its localization and regulation within the retina would shed light on the direction of retinal iron flux. The hormone hepcidin may regulate retinal Fpn, as it triggers Fpn degradation in the gut. Immunofluorescence was used to label Fpn in retinas of mice with 4 different genotypes (wild type; Fpn C326S, a hepcidin-resistant Fpn; hepcidin knockout; and ceruloplasmin/hephaestin double knockout). No significant difference in Fpn levels was observed in these retinas...
February 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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