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https://www.readbyqxmd.com/read/28632844/complement-mediated-regulation-of-apolipoprotein-e-in-cultured-human-rpe-cells
#1
Ping Yang, Nikolai P Skiba, Grace M Tewkesbury, Victoria M Treboschi, Peter Baciu, Glenn J Jaffe
PURPOSE: Complement activation is implicated in the pathogenesis of age-related macular degeneration (AMD). Apolipoprotein E (ApoE) and complement activation products such as membrane attack complex (MAC) are present in eyes of individuals with AMD. Herein, we investigated the effect of complement activation on induction of ApoE accumulation in human retinal pigment epithelial (RPE) cells. METHODS: Cultured human RPE cells were primed with a complement-fixing antibody followed by treatment with C1q-depleted (C1q-Dep) human serum to elicit alternative pathway complement activation...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28631484/ocular-pharmacokinetics-of-therapeutic-antibodies-given-by-intravitreal-injection-estimation-of-retinal-permeabilities-using-a-3-compartment-semi-mechanistic-model
#2
Laurence A Hutton-Smith, Eamonn A Gaffney, Helen M Byrne, Philip K Maini, Kapil Gadkar, Norman Alan Mazer
Intravitreally (IVT) injected macromolecules for the treatment of age-related macular degeneration must permeate through the inner limiting membrane (ILM) into the retina and through the retinal pigment epithelium (RPE) to enter the choroid. A quantitative understanding of intraocular transport mechanisms, elimination pathways and the effect of molecular size, is currently incomplete. We present a semi-mechanistic, 3-compartment (retina, vitreous and aqueous) pharmacokinetic (PK) model, expressed using linear ordinary differential equations (ODEs), to describe the molecular concentrations following a single IVT injection...
June 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28630787/evaluation-of-aflibercept-treatment-responses-in-eyes-with-bevacizumab-ranibizumab-resistant-wet-age-related-macular-degeneration
#3
Tuncay Topal, Taner Kar, Yıldıray Yıldırım, Sercan Koray Sağdıç, Cihan Büyükavşar, Abdullah Kaya, Ali Ayata, Murat Sönmez, Melih Hamdi Ünal
OBJECTIVES: To evaluate anatomic and functional results after switching from intravitreal bevacizumab or ranibizumab treatment to aflibercept for wet (neovascular) age-related macular degeneration. MATERIALS AND METHODS: This retrospective study included 22 eyes of 22 patients resistant to treatment with at least 6 injections of bevacizumab or ranibizumab. The first three injections had been applied monthly, the others pro re nata (PRN). Outcome measures were follow-up period, injection number, best corrected visual acuity (BCVA), central retinal thickness (CRT) and pigment epithelial detachment (PED) height...
June 2017: Turkish Journal of Ophthalmology
https://www.readbyqxmd.com/read/28628761/loss-of-function-of-p2x7-receptor-scavenger-activity-in-aging-mice-a-novel-model-for-investigating-the-early-pathogenesis-of-age-related-macular-degeneration
#4
Kirstan A Vessey, Ben J Gu, Andrew I Jobling, Joanna A Phipps, Ursula Greferath, Mai X Tran, Michael A Dixon, Paul N Baird, Robyn H Guymer, James S Wiley, Erica L Fletcher
Age-related macular degeneration (AMD) is a leading cause of irreversible, severe vision loss in Western countries. Recently, we identified a novel pathway involving P2X7 receptor scavenger function expressed on ocular immune cells as a risk factor for advanced AMD. In this study, we investigate the effect of loss of P2X7 receptor function on retinal structure and function during aging. P2X7-null and wild-type C57bl6J mice were investigated at 4, 12, and 18 months of age for macrophage phagocytosis activity, ocular histological changes, and retinal function...
June 16, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28626601/long-term-efficacy-of-gmp-grade-xeno-free-hesc-derived-rpe-cells-following-transplantation
#5
Trevor J McGill, Osnat Bohana-Kashtan, Jonathan W Stoddard, Michael D Andrews, Neelay Pandit, Lior R Rosenberg-Belmaker, Ofer Wiser, Limor Matzrafi, Eyal Banin, Benjamin Reubinoff, Nir Netzer, Charles Irving
PURPOSE: Retinal pigment epithelium (RPE) dysfunction underlies the retinal degenerative process in age-related macular degeneration (AMD), and thus RPE cell replacement provides an optimal treatment target. We characterized longitudinally the efficacy of RPE cells derived under xeno-free conditions from clinical and xeno-free grade human embryonic stem cells (OpRegen) following transplantation into the subretinal space of Royal College of Surgeons (RCS) rats. METHODS: Postnatal (P) day 20 to 25 RCS rats (n = 242) received a single subretinal injection of 25,000 (low)-, 100,000 (mid)-, or 200,000 (high)-dose xeno-free RPE cells...
June 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28625537/the-developmental-stage-of-adult-human-stem-cell-derived-retinal-pigment-epithelium-cells-influences-transplant-efficacy-for-vision-rescue
#6
Richard J Davis, Nazia M Alam, Cuiping Zhao, Claudia Müller, Janmeet S Saini, Timothy A Blenkinsop, Francesca Mazzoni, Melissa Campbell, Susan M Borden, Carol J Charniga, Patty L Lederman, Vanessa Aguilar, Michael Naimark, Michael Fiske, Nathan Boles, Sally Temple, Silvia C Finnemann, Glen T Prusky, Jeffrey H Stern
Age-related macular degeneration (AMD) is a common cause of central visual loss in the elderly. Retinal pigment epithelial (RPE) cell loss occurs early in the course of AMD and RPE cell transplantation holds promise to slow disease progression. We report that subretinal transplantation of RPE stem cell (RPESC)-derived RPE cells (RPESC-RPE) preserved vision in a rat model of RPE cell dysfunction. Importantly, the stage of differentiation that RPESC-RPE acquired prior to transplantation influenced the efficacy of vision rescue...
June 13, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28622396/mutant-fibulin-3-causes-proteoglycan-accumulation-and-impaired-diffusion-across-bruch-s-membrane
#7
Astrid Zayas-Santiago, Samuel D Cross, James B Stanton, Alan D Marmorstein, Lihua Y Marmorstein
Purpose: The mutation R345W in EFEMP1 (fibulin-3) causes macular degeneration. This study sought to determine whether proteoglycan content and diffusion across Bruch's membrane are altered in Efemp1ki/ki mice carrying this mutation or in Efemp1-/- mice. Methods: Proteoglycans in mouse Bruch's membranes were stained with Cupromeronic Blue (CB). Heparan sulfated proteoglycan (HSPG) and chondroitin/dermatan sulfate proteoglycan (C/DSPG) distributions were visualized following treatments with chondroitinase ABC (C-ABC) or nitrous acid...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28615726/microfluidic-co-cultures-of-retinal-pigment-epithelial-cells-and-vascular-endothelial-cells-to-investigate-choroidal-angiogenesis
#8
Li-Jiun Chen, Shuntaro Ito, Hiroyuki Kai, Kuniaki Nagamine, Nobuhiro Nagai, Matsuhiko Nishizawa, Toshiaki Abe, Hirokazu Kaji
Angiogenesis plays a critical role in many diseases, including macular degeneration. At present, the pathological mechanisms remain unclear while appropriate models dissecting regulation of angiogenic processes are lacking. We propose an in vitro angiogenesis process and test it by examining the co-culture of human retinal pigmental epithelial cells (ARPE-19) and human umbilical vein endothelial cells (HUVEC) inside a microfluidic device. From characterisation of the APRE-19 monoculture, the tight junction protein (ZO-1) was found on the cells cultured in the microfluidic device but changes in the medium conditions did not affect the integrity of monolayers found in the permeability tests...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28613221/clinicopathologic-correlation-of-retinal-angiomatous-proliferation-treated-with-ranibizumab
#9
Alison H Skalet, Audra K Miller, Michael L Klein, Andreas K Lauer, David J Wilson
PURPOSE: To describe histopathologic features of an eye with retinal angiomatous proliferation (RAP) secondary to age-related macular degeneration treated with serial ranibizumab injections and to correlate these findings with spectral domain optical coherence tomography. METHODS: Histopathologic features from serial sections through the globe of a 93-year-old man with age-related macular degeneration were studied and compared with spectral domain optical coherence tomography images obtained 7 weeks before his death...
April 26, 2017: Retina
https://www.readbyqxmd.com/read/28613215/correlation-between-preoperative-en-face-optical-coherence-tomography-of-photoreceptor-layer-and-visual-prognosis-after-macular-hole-surgery
#10
Kiyoung Kim, Eung Suk Kim, Yonguk Kim, Seung-Young Yu, Hyung Woo Kwak
PURPOSE: To investigate the correlation between preoperative en face spectral domain optical coherence tomography findings of the photoreceptor layer with restoration of foveal microstructure and visual acuity in repaired macular holes. METHODS: Medical records of 106 patients with surgically closed macular holes were retrospectively reviewed. Preoperative OCT slabs of the external limiting membrane (ELM) and ellipsoid zone (EZ) were generated using embedded tools...
May 22, 2017: Retina
https://www.readbyqxmd.com/read/28613213/ellipsoid-zone-mapping-and-outer-retinal-assessment-in-stargardt-disease
#11
Sruthi Arepalli, Elias I Traboulsi, Justis P Ehlers
PURPOSE: To quantify and correlate ellipsoid zone and photoreceptor outer segment changes with visual acuity in Stargardt disease. METHODS: An institutional review board-approved study of 32 eyes with Stargardt disease was performed. After spectral domain optical coherence tomography, the macular cube was exported into a novel analysis tool and volumetric assessment from the ellipsoid zone to the retinal pigment epithelium was performed. Using this information, mapping was completed with en face representation of the height between the ellipsoid zone and retinal pigment epithelium...
June 6, 2017: Retina
https://www.readbyqxmd.com/read/28607377/amyloid-%C3%AE-peptides-overexpression-in-retinal-pigment-epithelial-cells-via-aav-mediated-gene-transfer-mimics-amd-like-pathology-in-mice
#12
Tuhina Prasad, Ping Zhu, Amrisha Verma, Paramita Chakrabarty, Awilda M Rosario, Todd E Golde, Qiuhong Li
Age-related macular degeneration (AMD) is a progressive retinal neurodegenerative disorder characterized by extracellular deposits known as drusen. A major constituent of drusen deposits are Alzheimer disease-associated amyloid β (Aβ) peptides. To understand the etiology of Aβ proteostasis in AMD, we delivered recombinant adeno-associated virus (AAV) encoding Aβ42 and Aβ40 peptides fused to BRI2 protein by intraocular injection in C57BL/6J mice. Endogenous protease cleavage of such constructs leads to production of secreted Aβ42 and Aβ40 respectively...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28604541/high-dose-high-frequency-aflibercept-for-recalcitrant-neovascular-age-related-macular-degeneration
#13
Qi Sheng You, Raouf Gaber, Amit Meshi, Hema L Ramkumar, Mostafa Alam, Ilkay Kilic Muftuoglu, William R Freeman
PURPOSE: To determine the efficacy of monthly (0.1 mL/4 mg) aflibercept for refractory neovascular age-related macular degeneration (wet age-related macular degeneration). METHODS: This was a retrospective interventional case series in which patients with wet age-related macular degeneration were treated with stepwise dose escalation. Nonvitrectomized patients resistant to monthly (Q4W) ranibizumab/bevacizumab were switched to 2 mg aflibercept every 8 weeks. With resistance, they were escalated to Q4W 2 mg aflibercept, then Q4W 4 mg (high dose high frequency, 4Q4W) aflibercept...
June 9, 2017: Retina
https://www.readbyqxmd.com/read/28602950/on-phagocytes-and-macular-degeneration
#14
REVIEW
Xavier Guillonneau, Chiara M Eandi, Michel Paques, José-Alain Sahel, Przemyslaw Sapieha, Florian Sennlaub
Age related macular degeneration (AMD) is a complex multifactorial disease caused by the interplay of age and genetic and environmental risk factors. A common feature observed in early and both forms of late AMD is the breakdown of the physiologically immunosuppressive subretinal environment and the protracted accumulation of mononuclear phagocytes (MP). We here discuss the origin and nature of subretinal MPs, the mechanisms that lead to their accumulation, the inflammatory mediators they produce as well as the consequences of their chronic presence on photoreceptors, retinal pigment epithelium and choroid...
June 7, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/28600982/altered-bioenergetics-and-enhanced-resistance-to-oxidative-stress-in-human-retinal-pigment-epithelial-cells-from-donors-with-age-related-macular-degeneration
#15
Deborah A Ferrington, Mara C Ebeling, Rebecca J Kapphahn, Marcia R Terluk, Cody R Fisher, Jorge R Polanco, Heidi Roehrich, Michaela M Leary, Zhaohui Geng, James R Dutton, Sandra R Montezuma
Age-related macular degeneration (AMD) is the leading cause of blindness among older adults. It has been suggested that mitochondrial defects in the retinal pigment epithelium (RPE) underlies AMD pathology. To test this idea, we developed primary cultures of RPE to ask whether RPE from donors with AMD differ in their metabolic profile compared with healthy age-matched donors. Analysis of gene expression, protein content, and RPE function showed that these cultured cells replicated many of the cardinal features of RPE in vivo...
June 1, 2017: Redox Biology
https://www.readbyqxmd.com/read/28600524/disruption-of-retinal-pigment-epithelial-cell-properties-under-the-exposure-of-cotinine
#16
Xiao-Yu Zhang, Tsz Kin Ng, Mårten Erik Brelén, Kwok Ping Chan, Di Wu, Jasmine Sum Yee Yung, Di Cao, Yumeng Wang, Shaodan Zhang, Sun On Chan, Chi Pui Pang
Cigarette smoking is a major risk factor for age-related macular degeneration (AMD), in which progressive retinal pigment epithelial (RPE) cell degeneration is a major pathological change. Nicotine is a major biologically active component in cigarette smoke. It is continuously catabolized into cotinine, which has longer half-life and higher concentration in tissue cells and fluids. Here we hypothesized that continuous exposure of cotinine has more potent effects on human RPE cell properties than nicotine. Human RPE cell line (ARPE-19) was treated continuously with 1-2 µM of nicotine and/or cotinine for 7 days...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28600515/evaluation-of-intraretinal-migration-of-retinal-pigment-epithelial-cells-in-age-related-macular-degeneration-using-polarimetric-imaging
#17
Masahiro Miura, Shuichi Makita, Satoshi Sugiyama, Young-Joo Hong, Yoshiaki Yasuno, Ann E Elsner, Shigeo Tamiya, Rintaro Tsukahara, Takuya Iwasaki, Hiroshi Goto
The purpose of the present study was to evaluate the intraretinal migration of the retinal pigment epithelium (RPE) cells in age-related macular degeneration (AMD) using polarimetry. We evaluated 155 eyes at various AMD stages. Depolarized light images were computed using a polarization-sensitive scanning laser ophthalmoscope (PS-SLO), and the degree of polarization uniformity was calculated using polarization-sensitive optical coherence tomography (OCT). Each polarimetry image was compared with the corresponding autofluorescence (AF) images at 488 nm (SW-AF) and at 787 nm (NIR-AF)...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28596286/one-year-outcome-of-intravitreal-ziv-aflibercept-therapy-for-non-responsive-neovascular-age-related-macular-degeneration
#18
Imoro Zeba Braimah, Komal Agarwal, Ahmad Mansour, Jay Chhablani
AIM: To evaluate 12-month outcome of intravitreal ziv-aflibercept (IVZ) therapy in eyes with neovascular age-related macular degeneration (nAMD) that are non-responsive to bevacizumab and ranibizumab. METHODS: This retrospective study included 16 eyes (14 patients) with nAMD who were on prior treatment with bevacizumab and ranibizumab and were treated with as-needed IVZ (1.25 mg/0.05 mL) for 12 months. The primary outcome measure was the mean change in best corrected visual acuity (BCVA) and secondary outcome measures included mean change in central macular thickness (CMT), retinal pigment epithelial detachment (RPED) heights, longest treatment free interval, presence of subretinal fluid (SRF) and intraretinal fluid (IRF) and adverse events...
June 8, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28593392/multimodal-imaging-and-functional-correlations-identify-unusual-cases-of-macular-retinal-pigment-epithelium-hypopigmentation-occurring-without-functional-loss
#19
E Boulanger-Scemama, J Akesbi, S Tick, S Mohand-Said, J-A Sahel, I Audo
PURPOSE: Patients with unusual macular retinal pigment epithelium (RPE) hypopigmentation are described and analyzed using retinal multimodal imaging. METHODS: We report three cases of patients with unilateral (2) or bilateral (1) macular lesions discovered incidentally on fundoscopy. A comprehensive ophthalmic examination including visual acuity, fundoscopy, spectral-domain optical coherence tomography (SD-OCT), short-wavelength light and near-infrared autofluorescence, fluorescein angiography, microperimetry, multifocal electroretinogram, adaptive optics (AO), and OCT-angiography (OCT-A) has been performed...
June 7, 2017: Documenta Ophthalmologica. Advances in Ophthalmology
https://www.readbyqxmd.com/read/28590316/recurrence-of-choroidal-neovascularization-lesion-activity-after-aflibercept-treatment-for-age-related-macular-degeneration
#20
Tomotaka Wakazono, Kenji Yamashiro, Akio Oishi, Sotaro Ooto, Hiroshi Tamura, Yumiko Akagi-Kurashige, Masayuki Hata, Ayako Takahashi, Akitaka Tsujikawa, Nagahisa Yoshimura
PURPOSE: To examine the recurrence rate of choroidal neovascularization (CNV) lesion activity in age-related macular degeneration (AMD) and associated factors after 1-year aflibercept treatment. METHODS: Age-related macular degeneration eyes with 1-year aflibercept fixed-regimen treatment and a follow-up period of at least 18 months from the initial aflibercept injection for treatment-naive exudative AMD were retrospectively evaluated. The recurrence rate was examined...
January 11, 2017: Retina
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