bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individual characters affected by cataract in the riverside population of the Tapajós River, in Pará
Authors: Caramel Lais Raphaelli , Simão Giovanna Oncala , Czezacki Alexandre Scramin , Mont’Alvão Vanessa Giffoni Braga , França Jhenifer Nataly Moura , Gobbo Luísa da Cunha , Reis Bruna Albertini , Ricioli Isabella Soares , Olavarria Gustavo de Campos , de Souza Marianne Benedicto , Beckedorff Otto Albuquerque , Pizzato Rebecca de Souza , Carmo Thiago José Delfraro , Succi Fabiana Moreira Passos , Minussi Luíza Abreu , Abreu Elvira Barbosa 
Published: December 2019

AbstractPurposeThe study search a prevalence Cataracts profile in the Riverside Population of the Tapajós River, in Pará. In view of this disease, it is the largest cause of reversible blindness in the world, accountable of 47.8% of the cases and of great social relevance because it impacts the quality of life.MethodsA prospective, observational, analytical, cross‐sectional, ecological study based on the review of medical records in the voluntary project Barco de Saúde São Leopoldo Mandic. The cataract cases were classified according to the LOCSIII system.ResultsOf these, 56.6% are males and 43.39% are females. The proportion between each age group was: 0.62% (10–19 years); 1.88% (30–39 years); 16.98% (40–49 years); 32.7% (50–59 years); 24.5% (60–69 years); 19.49% (70–79 years) and, 3.77% (80–89 years). The prevalence of pseudophakia among the other diagnoses was 2.64%. The mean visual acuity with correction in each age group was: 20/30 (10–19 years); 20/25 (30–39 years); 20/25 (40–49 years); 20/50 (50–59 years); 20/60 (60–69 years); 20/110 (70–79 years) and 20/250 (80–89 years).ConclusionsThe incidence of cataract in north of Brazil is high, when compared, for example, with the USA, where the overall prevalence is only 8.6%. The number of pseudophakia is low (2.64%). The beginning of appearance is untimely and the proportion of cases is higher than the resto of the country.
Pharmacokinetics of angiotensin‐receptor blocker in cyclodextrin nanoparticle eye drops in rabbits
Authors: Kallab Martin , Schützenberger Kornelia , Hommer Nikolaus , Jasmin Schäfer Bhavapriya , Tan Aimin , Jansook Phatsawee , Stefansson Einar , Garhöfer Gerhard 
Published: December 2019

AbstractPurposeCyclodextrin nanoparticles form water‐soluble complexes with lipophilic and poorly water‐soluble drugs and thus can greatly improve drug transport from the ocular surface to the posterior eye segment. The aim of the current study was to evaluate the ocular pharmacokinetics and biodistribution of two newly developed □‐cyclodextrin based angiotensin receptor antagonist formulations for topical administration: cyclodextrin‐Irbesartan 1.5% and cyclodextrin‐Candesartan 0.15%.Methods59 rabbits were included in the study to receive one of the two study drugs. For each drug group, single and multiple dose pharmacokinetics were performed in a randomized fashion: Single dose rabbits were euthanized 0.5, 1.5, 3 or 6 hours post eye drop administration, whereas multiple dose animals were dosed for 5 days twice daily. Pharmacokinetic parameters including maximal drug concentration (Cmax) and time of maximal drug concentrations (Tmax) for single dosing and mean concentrations for multiple dosing were calculated for aqueous humor (AH) and retina/choroid (RT). Analysis was done using LC‐MS/MS.ResultsTopical administration of the study drugs was well tolerated. Single dose Irbesartan eye drop administration led to a RT Cmax of 251 ng/g ± 143 ng/g at 0.5 hours whereas in the AH a Cmax of 121 ng/g ± 69 ng/g was reached at 3 hours post instillation. For single dose Candesartan eye drops, RT Cmax was 63 ng/g ± 39 ng/g at 0.5 hours after application. AH reached a Cmax of 30 ng/g ± 14 ng/g at the 3 hours time point. For multiple dosing mean RT concentration reached 338 ng/g ± 124 ng/g for Irbesartan and 36 ng/g ± 10 ng/g for Candesartan, whereas mean AH concentrations were 231 ng/g ± 68 ng/g and 70 ng/g ± 22 ng/g, respectively.ConclusionsThe present data confirm that cyclodextrin based Candesartan and Irbesartan eye drops deliver drugs to the posterior pole of the eye in biologically relevant concentrations.
Increased lipofuscin accumulation associated with disturbed mitophagy in NRF2/PGC1α double knockout mice
Authors: Sridevi Gurubaran Iswariyaraja 
Published: December 2019

AbstractPurposeOxidative stress and mitochondrial damage are long protruded cause of detrimental aggregation diseases including age‐related macular degeneration. We recently reported elevated levels of oxidative stress markers, damaged mitochondria, accumulated lipofuscin and drusen like structures in retinal pigment epithelial cells (RPE) of NRF2/PGC1α double knockout mice model.MethodsImmunostained RPE samples from one‐year old NRF2/PGC1α and age matched wild type mice were used for confocal microscopy analysis.ResultsLipofuscin accumulation associated with deficiency of mitophagy in RPE cells of NRF2/PGC1α double knockout mice. Immunohistochemical analysis revealed high staining levels of autophagosome marker, microtubule‐associated proteins 1A/1B light chain 3B (LC3B) and mitophagy markers, PTEN‐induced putative kinase 1 (PINK1) and E3 ubiquitin ligase (PARKIN) on damaged mitochondria. Moreover, high levels of late autolysosomal fusion protein Rab7 accumulated in the peri‐nuclear space of RPE cells with increasing incidental colocalization of lipofuscin.ConclusionOur study reveals that fusion of lysosomes and autophagosomes occurs, but mitophagy flux is disturbed in lipofuscin loaded RPE cells of NRF2/PGC1α double knockout mice.
OCT‐angiography: Mydriatic phenylephrine and tropicamide do not influence retinal microvasculature in the macula and peripapillary region
Authors: Hohberger Bettina , Müller Meike , Hosari Sami , Mardin Christian 
Published: December 2019

AbstractPurposeOptical Coherence Tomography Angiography (OCT‐A) enables visualization of retinal microcirculation. As a potential influence of mydriatic eye drops on retinal vessels was proposed, purpose of the study was to investigate the influence of phenylephrine and tropicamide on macula and peripapillary microcirculation measured with en face OCT‐A.Methods30 eyes of 30 healthy persons were measured by en face OCT‐A (Heidelberg OCT II Spectralis, Germany). Scans of the macula (subdivided: 12 sectors) and peripapillary region (subdivided: 4 sectors) were performed before and 30 min after local application of phenylephrine 5% and tropicamide 0.5%. Vessel density (VD) was quantified in three retinochoroidal layers (superficial vascular plexus (SVP), deep capillary plexus (DCP), intermediate capillary plexus (ICP)). Data analysis was done by the Erlangen‐Angio‐Tool.Results(1) Mean VD was 33.03 ± 3.1 (SVP), 23.53 ± 2.9 (ICP) and 25.48 ± 4.2 (DCP) before and 33.15 ± 2.9 (SVP), 23.74 ± 2.9 (ICP) and 25.82 ± 4.0 (DCP) during mydriasis. (2) Sectorial analysis showed a range of 30.63 ± 2.9–34.45 ± 2.9 (before) and 31.04 ± 2.9–34.34 ± 2.7 (during mydriasis) in SVP, 22.61 ± 2.9–24.93 ± 3.2 (before) and 22.75 ± 2.5–25.20 ± 3.0 (during mydriasis) in ICP and 24.56 ± 4.7–26.45 ± 3.4 (before) and 25.00 ± 4.1–27.07 ± 3.5 (during mydriasis) in DCP. (3) No differences between overall and sectorial VD before and after mydriatic eyedrops were observed (p>0.05). (4) Peripapillary region showed a mean VD of 31.82 ± 3.8 before and 31.59 ± 4.3 during mydriasis. Sectorial analysis of VD yielded a range of 31.04 ± 4.1–32.65 ± 3.8 (before) and 30.98 ± 4.4–31.89 ± 4.1 (during mydriasis). (5) Peripapillary VD was not statistically different during mydriasis compared to without (p>0.05).ConclusionPhenylephrine 5% and tropicamide 0.5% do not influence retinal microcirculation in macula and peripapillary region. Thus, OCT‐A can be done in mydriasis in order to enhance imaging process and quality of the scans.
Targeted genome sequencing of negative and positive human papillomavirus induced conjunctival carcinomas
Authors: Ramberg Ingvild , Toft Peter , Jensen David , von Buchwald Christian , Cilius Nielsen Finn , Funding Mikkel , Heegaard Steffen 
Published: December 2019

AbstractPurposeTo perform a comprehensive targeted genome sequencing of premalignant and malignant conjunctival squamous cell carcinomas in order to elucidate the genetic background of these tumours.MethodsDue to the scant knowledge of the mutational landscape in conjunctival carcinomas, we performed next‐generation sequencing of 509 genes commonly affected in human cancers. We sequenced a total of 110 tumours; 31 invasive carcinomas, 55 preinvasive and 24 coupled recurrent tumours. All cases were investigated for presence of human papillomavirus (HPV) by p16 immunohistochemistry, messenger RNA in situ hybridisation and HPV DNA PCR, and HPV positive tumours were genotyped by sequencing.Results21.4 % of the tumours were HPV positive. High‐risk HPV16 was the most commonly detected genotype (70%). There was an average of 9 mutations identified in each tumour. C to T substitutions at pyrimidine sites leading to missense mutations were the most common type of mutations. HPV negative tumours frequently harboured mutations in FGFR2, IGF1R, and EP400, whereas HPV positive tumours most frequently harboured mutations in the FOS, AKT2 and mTOR genes.ConclusionsUltraviolet radiation (UV)‐induced signature mutations were found in both HPV positive and HPV negative tumours. Different genes were affected in tumours harbouring high‐risk HPV positive tumours compared to HPV negative tumours.
The ability of eye tracking perimetry to detect glaucoma
Authors: Tatham Andrew , McClean Pam , Murray Ian , McTrusty Alice , Harry Brash , Brian Fleck , Minns Robert 
Published: December 2019

AbstractPurposeTo examine the diagnostic ability of saccadic vector optokinetic perimetry (SVOP), a new eye tracking perimeter, by assessing its capacity to differentiate healthy and glaucomatous participants, and to compare performance to standard automated perimetry (SAP).MethodsA prospective case‐control study including patients with glaucoma and healthy volunteers recruited from the glaucoma clinic at a university hospital and from the Scottish Health Research Register (SHARE). Participants underwent a comprehensive ophthalmic examination and performed SAP and SVOP in both eyes with the order of testing randomised.Results61 eyes of 31 participants with glaucoma and 47 eyes of 24 healthy participants were included in the study. Average SAP mean deviation (MD) in glaucomatous eyes was ‐8.72 ± 7.37 dB, with average SAP and SVOP sensitivities of 23.28 ± 0.89 dB and 22.1 ± 4.25 dB respectively. There was strong correlation between average SAP and SVOP sensitivities (r = 0.951 , P<0.001). On average, SAP sensitivity was 1.16 ± 1.43 dB higher than SVOP sensitivity, with 95% limits of agreement of ‐1.64 to 3.96 dB. SVOP average sensitivity had excellent ability to differentiate healthy and glaucomatous eyes with an AUC of 0.90 (95% CI 0.84 to 0.96), which was not significantly different to the performance of SAP average sensitivity (AUC = 0.92, 95% CI .0.86 to 0.97, P = 0.60) (Figure 6). SVOP had 85.2% sensitivity for 80% specificity, compared to 86.9% sensitivity for 80% specificity for SAP.ConclusionsThe results of this study suggest that eye tracking perimetry using SVOP could offer a feasible alternative to SAP for detection of glaucoma. Overall, there was good agreement between differential light sensitivity values measured using SVOP and those measured using SAP, and average SVOP and SAP sensitivities had similarly good ability to differentiate glaucomatous and healthy eyes.
The Influence of stereopsis on ability to perform simulated cataract surgery
Authors: Tatham Andrew , Dutton James , Watkins Alice , Dhillon Baljean 
Published: December 2019

AbstractBackgroundThe purpose of this study was to determine whether impaired or absent stereopsis affects ability to perform simulated microsurgical tasks.MethodsA prospective randomized cross‐over study including 12 medical students. Visual acuity and stereoacuity were measured for all subjects. A band pass filter was placed over the non‐dominant eye to reduce stereoacuity to 150 seconds of an arc (partial stereopsis) or the non‐dominant eye was completely occluded (absent stereopsis). Participants completed a computerized surgical simulator task three times with the order of testing randomized (normal stereopsis, absent stereopsis and partial stereopsis). The task involved forceps to grasp and position objects in the anterior chamber. Outcomes included area of ocular injury, time to task completion and overall score.ResultsOcular damage area was significantly worse when stereopsis was impaired to 150 seconds of an arc (p = 0.002), and worse still when stereopsis was absent (p < 0.001 for normal versus absent stereopsis and p = 0.005 for impaired versus absent stereopsis). The median ocular damage area was 3.55 mm2 (IQ range 1.21 to 5.88 mm2) with normal stereopsis, increasing to 6.10 mm2 (IQ range 3.96 to 12.47 mm2) with stereopsis reduced to 150 seconds of an arc and to 9.25 mm2 (IQ range 4.93 to 18.70 mm2) with no stereopsis. Time taken to complete the task increased and overall score decreased as stereopsis was reduced. Overall score decreased from 53% (IQ range 22.5 to 82%) under normal stereopsis to 0% (0 to 43.5%) with absent stereopsis.ConclusionImpaired stereopsis was associated with worse microsurgical performance which may have implications for surgical training. Absence of stereopsis resulted in worse performance than partial reduction in stereopsis.
Investigating the role of Gli1 in the development of choroidal neovascularisation
Authors: Marry Stephen , Xu Heping , Chen Mei 
Published: December 2019

AbstractUncontrolled inflammation in the retina can lead to fibrovascular membrane formation, which can cause severe structural damage to the retina thus leading to blindness. The pathogenesis of retinal fibrosis is not completely understood. Recent research has implicated the Hedgehog pathway transcription factor Gli1 in the development of fibrosis. This study aims to elucidate the role of Gli1 in the development of fibrovascular membranes in the retina utilising fluorescent reporter mice.Gli1CreERT2 mice were crossed with ROSA26TdTomato mice to produce Tomato x Gli1 crossbreeds. 6‐7 week old Heterozygous Tom x Gli1 mice received 100 mg/kg Tamoxifen daily (I.P.) for 5 days. Mice were monitored for 80 days to determine the duration Gli1‐Tomato expression. Eyes and other organs were collected for immunofluorescent staining. Tom x Gli1 mice received 4–5 laser burns per eye to induce choroidal neovascularisation and were monitored over 21 days to assess the expression of Gli1 in the injured retina using fundus imaging and immunofluorescent staining.Expression of Gli1‐Tomato was detected as far 80 days in the eye, predominantly in the choroid, sclera, cornea and ciliary body. Immunofluorescent staining displayed co‐expression of Gli1 with CD31+, NG2+, and Collagen 4+ blood vessels. Fundus imaging of CNV lesions displayed expression of Gli1‐tomato around the lesion. Immunostains of cryosections showed co‐expression of Gli1 with blood vessel markers in choroidal lesions.Gli1+ cells are expressed throughout the eye, most notably with blood vessels, and may contribute to the development of choroidal lesions in CNV.
A conditional Mitf mouse model of geographic atrophy (GA)
Authors: García Llorca Andrea , Sabaté Alba , Ögmundsdóttir Margrét Helga , Larue Lionel , Gesbert Franck , Steingrímsson Eiríkur , Eysteinsson Thor 
Published: December 2019

AbstractPurposeMice carrying different mutations in the microphthalmia‐associated transcription factor (Mitf) gene, affect the normal the retinal pigment epithelium (RPE) resulting in microphthalmia. The MitfK243R/K243R; Tyr::Cre mice have an induced conditional mutation, where Lysine 243 is mutated to Arginine, thus affecting DNA binding. The purpose of this study was to characterize eye development and function in these mutant mice. Our analysis shows retinal degeneration and slow progressive GA in the eyes of these mice.MethodsC5BL/6J (wild type) and MitfK243R/K243R; Tyr::Cre mice of 1, 3 and 12 months old were used in this study. Fundus and optical coherence tomography (OCT) images were taken from wild type and mutant mice. Retinal function was assessed by electroretinography (ERG). RNA isolation from posterior eye cups and reverse‐transcription quantitative PCR (RT‐qPCR) were done to analyze Mitf mRNA expression.ResultsBright field images indicate that eyes from B6‐MitfK243R; Tyr::Cre mice have alternating areas of severe hypo‐ and hyperpigmentation and vascular abnormalities. OCT images from 1 and 3 months old mutants demonstrated that some regions of the retina have the RPE, photoreceptor and neuronal layers intact, while neighboring areas show severe degeneration of these cell types. However, at one year of age the RPE, photoreceptor and outer retina layers are missing in the mutants. ERG recordings revealed that at 1 and 3 months old the mutants had significantly reduced (p < 0.05) photopic b‐wave, scotopic a‐ and b‐waves, while at 12 months old the mutant cone and rod ERG responses were flat or severely reduced compared to wild type. Gene expression analysis showed that Mitf expression was elevated in the mutants as compared to wild type, suggesting compensatory mechanisms.ConclusionsWe have found that mice with the MitfK243R conditional mutation driven by the Tyr::Cre driver may be the first mouse model of slow progressive retinal GA. This mutant shows similar characteristic as seen in human age‐related macular degeneration (AMD) and may therefore provide a model for that disease.
Activating an optogenetically engineered retina with a wearable headset in patients with retinitis pigmentosa
Authors: Chavas Joël , Boussahoul Nacer , Duport Damien , Galle Charlie , Galluppi Francesco , Blouin Laure , Burguière Pierre , Hardin Thomas , Shabestary Proshato , Gray David 
Published: December 2019

AbstractPurposeOptogenetics allows the expression of channelrhodopsins like ChrimsonR (ChR) in the retina of blind patients in order to confer light sensitivity to retinal ganglion cells (RGCs). However, ChR has a low sensitivity to light and is unlikely to be activated by ambient light. To activate ChR and to obtain a functional response from the RGCs, we developed and tested a wearable headset that delivers light stimulation to the human retina at an appropriate irradiance and wavelength.MethodsWe designed and constructed a wearable headset using electronics, optics, mechanics and software engineering. The proper range of light intensity required for the activation of ChR fused with tdTomato (ChRtdT) was tested on explanted retinas of non‐human primates (NHPs) transfected with AAV2.7m8‐ChRtdT. The ocular safety of exposure to 595 nm LED light following intravitreal injection of AAV2.7m8‐ChRdtT was assessed in rd1 mice, an established animal model for retinitis pigmentosa.ResultsActivation of ChRtdT in explanted retinas of NHPs transfected with AAV2.7m8‐ChRtdT showed that a minimum of 1015 photons/cm2/s (0.33 mW/cm2) of amber light was required to get a statistically significant electrophysiological response.In rd1 mice transfected with AAV2.7m8‐ChRtdT, fourteen days after exposure to 595‐nm LED light for 2 hours, no light‐related findings were identified in the retina at the highest intensity tested (nominal 1.7 × 1017 photons/cm2/s).As a result, our wearable headset provides a retinal irradiance up to 4 × 1016 photons/cm2/s for a period leading to a dose matching the one received by the retina of rd1 mouse exposed for 2 hours, a level shown to be safe for the retina.ConclusionOur medical device GS030‐MD was designed to send a light irradiance to the human retina both sufficient to activate ChRtdT and safe for the eye. GS030‐MD is currently being tested in combination with AAV2.7m8‐ChRtdT in the first‐in‐man PIONEER Phase I/II clinical trial.
Synthesis and application of magnetic nanoparticles (MNPs) in drug delivery to the retina
Authors: Bassetto Marco , Ajoy Moreno Daniel , Poulhes Florent , Marion Vincent , Dollfus Helene , Zelphati Olivier 
Published: December 2019

AbstractIntroductionThe development of an innovative drug delivery system to target, after topical administration, the retina with bioactive agents against retinal pathologies is a major challenge. Currently, the sole approach to target these tissues is through intravitreous injection, but this is not free from problematics such as severe side effects and rapid clearance of small molecules from the vitreous.PurposeWe aim to synthesize, develop and formulate a new magnetic nanoparticle‐mediated delivery technology that shall allow achieving needle‐free, anesthesia‐free delivery of active drugs to the retina after topical administration assisted by magnetic targeting.Methods

MNPs have been synthesized, physico‐chemically characterized and loaded with small organic drugs (valproic acid/Guanabenz).

The MNPs biocompatibility have been studied in vitro on retinal pigmented epithelium and photoreceptor cell lines and in vivo after topical administration.

The MNPs have been applied on mice under the influence of an external magnetic field to guide them towards the retina.

The in vivo histological and functional assays have been monitored to determine the biological effect of the treatment.

ResultsThe iron oxide‐based MNPs have spherical shape, a hydrodynamic size less than 150nm and they were not affected by the drug‐loading process. HPLC measurements demonstrate the high loading capacity of the MNPs and reproducibility of the method. Cell proliferation assays showed that MNPs are fully biocompatible.ConclusionsMNPs combined with magnetic targeting is a promising technology for the delivery of bioactive agents to the retina after topical, needle‐free administration.
Pharmacological modulation of the VCP/ERAD/proteasome axis rescues photoreceptor degeneration in P23H rhodopsin
Authors: Sen Merve , Kutsyr Oksana , Bolz Sylvia , Chou Tsui‐Fen , Deshaies Ray , Arango Gonzalez Blanca , Ueffing Marius 
Published: December 2019

AbstractPurposeOne of the most prevalent mutations in rhodopsin (Rh) causing autosomal dominant retinitis pigmentosa (adRP) RhP23H, results in its misfolding and its retention in the Endoplasmic Reticulum (ER). VCP is an ATP driven molecular checkpoint at the ER before these proteins are released from the ER towards plasma membrane. Misfolded proteins are selectively identified, retained at the ER and cleared by a process called ER‐associated degradation (ERAD). ERAD overload due to RhP23H misfolding causes cell death. As several pathways regulating protein homeostasis are associated with ERAD, we tested their specific impact on photoreceptor (PR) degeneration through pharmacological inhibition.MethodsOrganotypic cultures from RhP23H retinas of transgenic rats at PN9 cultured for 6 days and treated with different concentrations of pathway specific inhibitors: NMS‐873 interferes with quality control mechanisms by VCP inhibition; the proteasome inhibitor Bortezomib (BO) suppresses proteasomal degradation; the mannosidase inhibitor Kifunensine (KIF) blocks processing of glycoproteins, and Geldanamycin (GA) inhibits the protein‐folding mechanism in the ER. PR cell survival was assessed by counting cell rows and measuring the percentage of TUNEL‐positive cells. Rh distribution was checked using a specific antibody.ResultsVCP inhibitor caused strong and dose‐dependent protection at 5μM. Proteasome inhibition by BO significantly reduced the number of dying cells at 10μM. The number of PR cell rows in the ONL was increased by both. Only VCP inhibitor corrected aberrant inner segment distribution of Rh shifting it to physiological outer segment (OS). In contrary, KIF and GA accelerated PR cell degeneration.ConclusionsModulation of the VCP/ERAD/proteasome axis by inhibiting VCP and proteasome rescues PR cells in RhP23H. Inhibition of VCP activity establishes proper transport of Rh to the OS. These results strongly suggest that the VCP/ERAD/proteasome axis acts as a critical checkpoint in PR homeostasis.