The renin-angiotensin system and the retinal neurovascular unit: A role in vascular regulation and disease.
Abstract The retina is known to have a local renin-angiotensin system (RAS) and dysfunction in the RAS is often associated with diseases of the retinal vasculature that cause irreversible vision loss. Regulation of the retinal vasculature to meet the metabolic needs of the tissues occurs through a mechanism called neurovascular coupling, which is critical for maintaining homeostatic function and support for neurons. Neurovascular coupling is the process by which support cells, including glia, regulate blood vessel calibre and blood flow in response to neural activity. In retinal vascular diseases, this coupling me...
Source: Experimental Eye Research - August 10, 2019 Category: Opthalmology Authors: Phipps JA, Dixon MA, Jobling AI, Wang AY, Greferath U, Vessey KA, Fletcher EL Tags: Exp Eye Res Source Type: research
Influence of eye pigmentation on retinal degeneration in P23H and S334ter mutant rhodopsin transgenic rats.
Abstract Dark-rearing has been found to slow the rate of retinal degeneration in albino P23H but not S334ter mutant rhodopsin transgenic (Tg) rats. Since eye pigmentation has the same protective slowing effect as dark-rearing in RCS rats, we examined whether eye pigmentation has a comparable slowing effect in the different mutant rhodopsin Tg rats. Different lines of albino P23H and S334ter Tg rats on the Sprague-Dawley (SD) background were bred to Long-Evans (LE) rats to produce pigmented Tg rats. These were compared to albino Tg rats at postnatal days of different ages using the outer nuclear layer (ONL) as a mo...
Source: Experimental Eye Research - August 10, 2019 Category: Opthalmology Authors: Lowe RJ, Daniello KM, Duncan JL, Yang H, Yasumura D, Matthes MT, LaVail MM Tags: Exp Eye Res Source Type: research
Mineralocorticoid antagonists in the treatment of central serous chorioetinopathy: Review of the pre-clinical and clinical evidence.
Abstract Central serous chorioretinopathy (CSCR) is part of the pachychoroid spectrum disorders, characterized by serous retinal detachments, retinal pigment epithelium alterations and dilation of choroidal vessels. No consensus exists regarding the clinical classification and the physiopathogenic mechanisms of the disease, delaying the comprehension of the most optimal treatment options. An overactivation of the mineralocorticoid receptor (MR) pathway in the choroid/retina has been suggested in CSCR. Since, MR antagonists could target the affected RPE/choroid in CSCR and have shown to act as disease modifier drug...
Source: Experimental Eye Research - August 8, 2019 Category: Opthalmology Authors: Bousquet E, Zhao M, Daruich A, Behar-Cohen F Tags: Exp Eye Res Source Type: research
Inflammatory and cell death mechanisms induced by 7-ketocholesterol in the retina. Implications for age-related macular degeneration.
te;, Larráyoz IM Abstract This review will focus on the inflammatory and toxic mechanism of action of 7-ketocholesterol (7KCh) and the potential implications of its accumulation, especially in the retina. 7KCh is a pro-inflammatory oxysterol usually associated with oxidized lipoprotein deposits present in aged retinas. High amounts of 7KCh can be generated in situ in these lipoprotein deposits possibly through a free radical-mediated mechanism catalyzed by iron. 7KCh seems to activate several kinase signaling pathways that work via multiple transcription factors to induce cytokines and intracellular effecto...
Source: Experimental Eye Research - August 5, 2019 Category: Opthalmology Authors: Pariente A, Peláez R, Pérez-Sala Á, Larráyoz IM Tags: Exp Eye Res Source Type: research
Characterization of the cone-rod dystrophy retinal phenotype caused by novel homozygous DRAM2 mutations.
egui B, Pomares E Abstract Cone-rod dystrophies (CRD) are a group of Inherited Retinal Dystrophies (IRD) characterized by the primary involvement of cone photoreceptors, resulting in the degeneration of the central retina, or macula. Although there are more than 55 CRD genes, a considerable percentage of cases remain unsolved. In this context, the present study aimed to describe and characterize the phenoptype and the genetic cause of 3 CRD families from a cohort of IRD cases. Clinical evaluation in each patient was supported by a complete ophthalmological examination, including visual acuity measurement, fundus r...
Source: Experimental Eye Research - August 5, 2019 Category: Opthalmology Authors: Abad-Morales V, Burés-Jelstrup A, Navarro R, Ruiz-Nogales S, Méndez-Vendrell P, Corcóstegui B, Pomares E Tags: Exp Eye Res Source Type: research
Effect of acute and chronic aldosterone exposure on the retinal pigment epithelium-choroid complex in rodents.
Abstract Preclinical and clinical evidences show that aldosterone and/or mineralocorticoid receptor (MR) over-activation by glucocorticoids can be deleterious to the retina and to the retinal pigment epithelium (RPE)-choroid complex. However, the exact molecular mechanisms driving these effects remain poorly understood and pathological consequences of chronic exposure of the retina and RPE/choroid to aldosterone have not been completely explored. We aimed to decipher the transcriptomic regulation in the RPE-choroid complex in rats in response to acute intraocular aldosterone injection and to explore the consequenc...
Source: Experimental Eye Research - August 5, 2019 Category: Opthalmology Authors: Canonica J, Mehanna C, Bonnard B, Jonet L, Gelize E, Jais JP, Jaisser F, Zhao M, Behar-Cohen F Tags: Exp Eye Res Source Type: research
Shear stress modulates inner blood retinal barrier phenotype.
In conclusion, high shear stress and static flow, associated to impaired retinal circulation, may compromise the inner blood retinal barrier phenotype and barrier function in HRMEC. PMID: 31394104 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - August 5, 2019 Category: Opthalmology Authors: Molins B, Mora A, Romero-Vázquez S, Pascual-Méndez A, Rovira S, Figueras-Roca M, Balcells M, Adán A, Martorell J Tags: Exp Eye Res Source Type: research
Identification and characterization of a novel promoter variant in placental growth factor for neovascular age-related macular degeneration.
CONCLUSIONS: This study identified a rare, functional promoter variant in the PGF gene that increases PGF transcription activity and confers a 5-fold risk to neovascular AMD. PMID: 31377148 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - August 1, 2019 Category: Opthalmology Authors: Ma L, Ng TK, Chen H, Brelén ME, Lai TYY, Ho M, Tam POS, Young AL, Chen W, Tham CC, Pang CP, Chen LJ Tags: Exp Eye Res Source Type: research
Retinal proteome associated with bradykinin-induced edema.
This study characterizes the effects of BK on the ultrastructure and proteome of the rat retina. The effects of intravitreal injection of BK on retinal thickness and vascular ultrastructure in Sprague Dawley rats were analyzed and compared with the effects of VEGF using spectral-domain optical coherence tomography. At 24 h post intravitreal injection of BK or saline vehicle retina were harvested and solubilized proteins were analyzed by mass spectrometry-based proteomics. Proteins were identified using X!Tandem and spectral counts were used as a semiquantitative measurement of protein abundance. Proteins identified from ...
Source: Experimental Eye Research - July 24, 2019 Category: Opthalmology Authors: Murugesan N, Fickweiler W, Clermont AC, Zhou Q, Feener EP Tags: Exp Eye Res Source Type: research
Reduced humidity experienced by mice in vivo coincides with reduced outflow facility measured ex vivo.
Abstract Mice are routinely used to study aqueous humour dynamics. However, physical factors such as temperature and hydration affect outflow facility in enucleated eyes. This retrospective study examined whether differences in temperature and relative humidity experienced by living mice within their housing environment in vivo coincide with differences in outflow facility measured ex vivo. Facility data and environmental records were collected for one enucleated eye from 116 mice (C57BL/6J males, 9-14 weeks) at two institutions. Outflow facility was reduced when relative humidity was below the lower limit of 45% ...
Source: Experimental Eye Research - July 24, 2019 Category: Opthalmology Authors: Reina-Torres E, Bertrand JA, O'Callaghan J, Sherwood JM, Humphries P, Overby DR Tags: Exp Eye Res Source Type: research
Anti-apoptotic effect of interleukin-17 in a mouse model of oxygen-induced retinopathy.
Abstract Retinopathy of prematurity (ROP) is an important cause of visual loss in children born prematurely. Although the involvement of inflammation in the development of ROP is gaining increasing attention, the role of IL-17A in ROP progress remains unclear. The aim of this study was to assess the levels of IL-17A production in the mice model of oxygen-induced retinopathy (OIR) and elucidate its potential roles. Wild-type (WT) and IL-17A knockout (IL-17A-/-) mice were exposed to 75% O2 from postnatal day 7 (P7) to P12. Age-matched controls were maintained in room air. Primary Müller cells isolated from WT o...
Source: Experimental Eye Research - July 23, 2019 Category: Opthalmology Authors: Li N, Gao S, Wang J, Zhu Y, Shen X Tags: Exp Eye Res Source Type: research
Duloxetine protects against experimental diabetic retinopathy in mice through retinal GFAP downregulation and modulation of neurotrophic factors.
Abstract Diabetic retinopathy (DR) is recognized as one of the leading causes of blindness worldwide. Searching and validation for a novel therapeutic strategy to prevent its progress are promising. This work aimed to assess the retinal protective effects of duloxetine (DLX) in Alloxan-induced diabetic mice model. Animals were equally and randomly divided to four groups (eight mice per group); group 1: is the control group, 2: diabetic group, 3&4: diabetic and after 9 weeks received DLX for 4 weeks (15 mg/kg and 30 mg/kg), respectively. Quantitative real-time PCR (qPCR) analysis revealed nerve growth facto...
Source: Experimental Eye Research - July 22, 2019 Category: Opthalmology Authors: Bahr HI, Abdelghany AA, Galhom RA, Barakat BM, Arafa EA, Fawzy MS Tags: Exp Eye Res Source Type: research
Prolonged nearwork affects the ciliary muscle morphology.
er T Abstract There is evidence for a possible link between myopia development and near vision. We investigated the effect of prolonged nearwork on ciliary muscle (CM) morphology and accommodation in 18 myopic and 17 emmetropic subjects (age 19 to 25). The CM was imaged during far (0.25 D) and near vision (4 D) using optical coherence tomography (OCT), and accommodation to a step pulse (0.25 D-4 D-0.25 D, 15 s each) was assessed by eccentric infrared photorefraction before and after a 30-min reading task at 25 cm. OCT images were analyzed using a custom-developed semi-automatic segmentation algorithm to determ...
Source: Experimental Eye Research - July 20, 2019 Category: Opthalmology Authors: Wagner S, Schaeffel F, Zrenner E, Straßer T Tags: Exp Eye Res Source Type: research
Regional changes in the elastic properties of myopic Guinea pig sclera.
Abstract Biomechanical changes in the sclera likely underlie the excessive eye elongation of axial myopia. We studied the biomechanical characteristics of myopic sclera at the microscopic level using scanning acoustic microscopy (SAM) with 7-μm in-plane resolution. Guinea pigs underwent form-deprivation (FD) in one eye from 4 to 12 days of age to induce myopia, and 12-μm-thick scleral cryosections were scanned using a custom-made SAM. Two-dimensional maps of the bulk modulus (K) and mass density (ρ) were derived from the SAM data using a frequency-domain approach. We assessed the effect on K and ρ ex...
Source: Experimental Eye Research - July 19, 2019 Category: Opthalmology Authors: Hoang QV, Rohrbach D, McFadden SA, Mamou J Tags: Exp Eye Res Source Type: research
Effect of chronic topical latanoprost on the sclera and lamina cribrosa of form-deprived myopic Guinea pigs.
Abstract The purpose of this study was to investigate the effects of latanoprost, an ocular hypotensive prostaglandin analog, on scleral collagen fibers and laminar pores in myopic guinea pigs. Young guinea pigs underwent monocular form deprivation (FD; white plastic diffusers) from 14-days of age for 10-weeks. After the first week, FD eyes also received daily topical A) latanoprost (Lat, 0.005%, n = 5) or B) artificial tears (AT; n = 5). At the end of the treatment period, animals were sacrificed, eyes enucleated and optic nerve heads (ONH) excised to include a 4 mm diameter ring of surrounding sclera f...
Source: Experimental Eye Research - July 19, 2019 Category: Opthalmology Authors: El-Nimri NW, Yao M, Huerta A, Hoang M, Wildsoet CF Tags: Exp Eye Res Source Type: research
Serum metabolomics profiling and potential biomarkers of myopia using LC-QTOF/MS.
The objectives of this study were to identify serum biomarkers and investigate the metabolic alterations of myopia. The serum metabolomics profiling was investigated on 30 high myopia cases and 30 controls (without myopia) using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS), and an independent additional cohort including 20 cases and 19 controls were investigated to validate potential metabolite candidates for biomarkers. According to the metabolic differences, the myopia patients and controls could be divided into different clusters and nine metabolites were found to be closely correlated ...
Source: Experimental Eye Research - July 17, 2019 Category: Opthalmology Authors: Dai L, Yang W, Qin X, Li Y, Cao H, Zhou C, Wang Y Tags: Exp Eye Res Source Type: research
Temporal change of retinal nerve fiber layer reflectance speckle in normal and hypertensive retinas.
This study investigated temporal change of retinal nerve fiber layer (RNFL) reflectance speckle in retinas with ocular hypertensive (OHT) damage and in control retinas from untreated eyes. Experimental OHT damage to rat retinas was induced by laser photocoagulation of the trabecular meshwork. A series of 660 nm reflectance images was collected from isolated retinas at 10-sec intervals. Areas containing speckled texture were selected on nerve fiber bundles. Correlation coefficients between images with different imaging delays were calculated and plotted as a function of delay. To evaluate the temporal change of speckles, ...
Source: Experimental Eye Research - July 17, 2019 Category: Opthalmology Authors: Huang XR, Knighton RW, Spector YZ, Kong W, Qiao J Tags: Exp Eye Res Source Type: research
Ocular mucins in dry eye disease.
Abstract Dry eye disease is a common and multifactorial disease with a high prevalence worldwide. Water loss, reduced expression of glycocalyx mucins, and loss of goblet cells secreting gel-forming mucins are hallmarks of dry eye disease. Mucins are large and complex heavily glycosylated proteins. Their organization in the tear film remains unclear, but they play a key role to protect and maintain integrity of the ocular surface. Mice have been extremely valuable mammalian models with which to study ocular physiology and disease, and to evaluate eye therapies. Genetically modified mice and spontaneously occurring ...
Source: Experimental Eye Research - July 17, 2019 Category: Opthalmology Authors: Portal C, Gouyer V, Gottrand F, Desseyn JL Tags: Exp Eye Res Source Type: research
Ferroportin-mediated iron export from vascular endothelial cells in retina and brain.
Abstract Retinal iron accumulation has been implicated in the pathogenesis of age-related macular degeneration (AMD) and other neurodegenerative diseases. The retina and the brain are protected from the systemic circulation by the blood retinal barrier (BRB) and blood brain barrier (BBB), respectively. Iron levels within the retina and brain need to be tightly regulated to prevent oxidative injury. The method of iron entry through the retina and brain vascular endothelial cells (r&bVECs), an essential component of the BRB and BBB, is not fully understood. However, localization of the cellular iron exporter, fe...
Source: Experimental Eye Research - July 16, 2019 Category: Opthalmology Authors: Baumann BH, Shu W, Song Y, Simpson EM, Lakhal-Littleton S, Dunaief JL Tags: Exp Eye Res Source Type: research
Kir7.1 inwardly rectifying K+ channel is expressed in ciliary body non pigment epithelial cells and might contribute to intraocular pressure regulation.
da FV Abstract Inwardly rectifying K+ channel Kir7.1 is expressed in epithelia where it shares membrane localisation with the Na+/K+-pump. The ciliary body epithelium (CBE) of the eye is a determinant of intraocular pressure (IOP) through NaCl-driven fluid secretion of aqueous humour. In the present study we explored the presence Kir7.1 in this epithelium in the mouse and its possible functional role in the generation of IOP. Use heterozygous animals for total Kir7.1 knockout expressing β-galactosidase under the control of Kir7.1 promoter, identified the expression of Kir7.1 in non-pigmented epithelial cells ...
Source: Experimental Eye Research - July 15, 2019 Category: Opthalmology Authors: Burgos J, Villanueva S, Ojeda M, Cornejo I, Cid LP, Sepúlveda FV Tags: Exp Eye Res Source Type: research
Identification of novel RHO homozygous mutation in Chinese autosomal recessive retinitis pigmentosa patients.
Abstract Retinitis pigmentosa (RP) is a group of genetically heterogeneous retinal diseases with more than 80 identified causative genes to date. The RHO (rhodopsin, OMIM 180380) gene mutation is a hotspot mutation worldwide and is one of the few genes which can cause both autosomal-dominant RP (adRP) and autosomal-recessive RP (arRP). To explore the frequency of RHO mutations in Chinese populations, RP patients' samples from 72 unrelated Chinese families with uncertain inherited pattern were collected. Testing of RHO was conducted by NGS (next-generation sequencing) and followed by Sanger sequencing validation to...
Source: Experimental Eye Research - July 15, 2019 Category: Opthalmology Authors: Wang J, Xu D, Chen X, Zhu T, Liu Q, Wang F, Zhang J, Tian H, Gao F, Zhang J, Jin C, Xu J, Lu L, Xu GT Tags: Exp Eye Res Source Type: research
"Houston, we have a problem": "We are losing our eyesight".
"Houston, we have a problem": "We are losing our eyesight". Exp Eye Res. 2019 Jul 14;:107725 Authors: Wostyn P PMID: 31315025 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - July 14, 2019 Category: Opthalmology Authors: Wostyn P Tags: Exp Eye Res Source Type: research
Proteomics reveals a set of highly enriched proteins in epiretinal membrane compared with inner limiting membrane.
te; B Abstract Few data exist regarding the protein composition of idiopathic epiretinal membrane (iERM). In the present study we compared the proteome of epiretinal membrane of iERM with the proteome of the inner limiting membrane (ILM) of idiopathic macular hole (iMH). Twelve epiretinal membrane samples were obtained from patients with iERM undergoing therapeutic vitrectomy. Twelve ILM samples were obtained from patients with iMH and were used as controls. Proteomic analysis was conducted with discovery-based label-free quantitative nano-liquid chromatography - tandem mass spectrometry (LFQ nLC-MS/MS). Verificat...
Source: Experimental Eye Research - July 11, 2019 Category: Opthalmology Authors: Christakopoulos C, Cehofski LJ, Christensen SR, Vorum H, Honoré B Tags: Exp Eye Res Source Type: research
In vivo phenotypic and molecular characterization of retinal degeneration in mouse models of three ciliopathies.
Abstract Cilia are highly conserved and ubiquitously expressed organelles. Ciliary defects of genetic origins lead to ciliopathies, in which retinal degeneration (RD) is one cardinal clinical feature. In order to efficiently find and design new therapeutic strategies the underlying mechanism of retinal degeneration of three murine model was compared. The rodent models correspond to three emblematic ciliopathies, namely: Bardet-Biedl Syndrome (BBS), Alström Syndrome (ALMS) and CEP290-mediated Leber Congenital Amaurosis (LCA). Scotopic rodent electroretinography (ERG) was used to test the retinal function of mi...
Source: Experimental Eye Research - July 11, 2019 Category: Opthalmology Authors: Brun A, Yu X, Obringer C, Ajoy D, Haser E, Stoetzel C, Roux MJ, Messaddeq N, Dollfus H, Marion V Tags: Exp Eye Res Source Type: research
Clinical and genetic update of corneal dystrophies.
PMID: 31301286 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - July 10, 2019 Category: Opthalmology Authors: Lisch W, Weiss JS Tags: Exp Eye Res Source Type: research
Symmetry of folds in FEVR: A genotype-phenotype correlation study.
In conclusion, the majority of retinal folds extended completely and radially in the temporal peripheral retina. Patients with causative mutations in NDP, TSPAN12, or KIF11 were more likely to have bilaterally symmetrical severe retinopathy. In contrast, patients with LRP5 and FZD4 mutations displayed a relatively milder but broader spectrum of phenotypes and a higher frequency of asymmetry. PMID: 31299183 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - July 9, 2019 Category: Opthalmology Authors: Wang Z, Chen C, Sun L, Zhang A, Liu C, Huang L, Ding X Tags: Exp Eye Res Source Type: research
Light stress affects cones and horizontal cells via rhodopsin-mediated mechanisms.
m C Abstract Retinal degenerations are a major cause of blindness in human patients. The identification of endogenous mechanisms involved in neurodegeneration or neuroprotection helps to understand the response of the retina to stress and provides essential information not only for basic retinal physiology but also for defining molecular targets for neuroprotective strategies. Here we used excessive light exposure as a model system to study mechanisms of photoreceptor degeneration in mice. Using one wild type and four genetically modified mouse strains, we demonstrate that light exposure resulted not only in the d...
Source: Experimental Eye Research - July 7, 2019 Category: Opthalmology Authors: Samardzija M, Todorova V, Gougoulakis L, Barben M, Nötzli S, Klee K, Storti F, Gubler A, Imsand C, Grimm C Tags: Exp Eye Res Source Type: research
Real-time OCT guidance and multimodal imaging monitoring of subretinal injection induced choroidal neovascularization in rabbit eyes.
This study evaluates a novel multimodal imaging platform combining optical coherence tomography (OCT) and photoacoustic microscopy (PAM). Using real-time OCT guidance subretinal injection to induce and multimodality imaging system to monitor CNV over time in rabbit eyes. The significance of our work lies in providing the optimal setting and conditions to make use of the OCT image guided system to improve the consistency and reproducibility of experimental results in subretinal injection induced CNV model in rabbits. For the first time, this study successfully demonstrated the dual-modality PAM-OCT system, without using exo...
Source: Experimental Eye Research - July 6, 2019 Category: Opthalmology Authors: Li Y, Zhang W, Nguyen VP, Rosen R, Wang X, Xia X, Paulus YM Tags: Exp Eye Res Source Type: research
Inactive Cas9 blocks vitreous-induced expression of Mdm2 and proliferation and survival of retinal pigment epithelial cells.
Abstract Mouse double minute (MDM)2 single nucleotide polymorphism (SNP) 309G allele in the second promoter of MDM2 enhances vitreous-induced expression of Mdm2 and degradation of the tumor suppressor protein p53. This MDM2SNP309G contributes to certain cancer development and experimental proliferative vitreoretinopathy. The goal of this study is to discover a novel strategy to only block vitreous-induced expression of Mdm2 for preventing vitreous-induced cell proliferation and survival and thus find a potential novel strategy to treat proliferation-related diseases. We created two mutations (D10A and H840A) in St...
Source: Experimental Eye Research - July 3, 2019 Category: Opthalmology Authors: Chen N, Hu Z, Yang Y, Han H, Lei H Tags: Exp Eye Res Source Type: research
Elemental concentrations in Choroid-RPE and retina of human eyes with age-related macular degeneration.
This study was aimed to measure the concentrations of these elements and metals in choroid-RPE and retina of human donor eyes with and without age-related macular degeneration associated changes. Human cadaver donor eyeballs were obtained from the CU Shah eye bank, Sankara Nethralaya Eye Hospital, India, after removal of the cornea. 39 control and 51 AMD donor eyes were used in this study. Alabama grading was done on the histopathological sections to identify early and late age-related macular degeneration changes. Concentrations of lead, cadmium, chromium, cobalt, nickel, arsenic and selenium were determined in choroid-RP...
Source: Experimental Eye Research - July 1, 2019 Category: Opthalmology Authors: Aberami S, Nikhalashree S, Bharathselvi M, Biswas J, Sulochana KN, Coral K Tags: Exp Eye Res Source Type: research
Scleral surgical repair through the use of nanostructured fibrin/agarose-based films in rabbits.
sinos I, Campos F Abstract Scleral defects can result as a consequence of trauma, infectious diseases or cancer and surgical repair with allogeneic scleral grafts can be required. However, this method has limitations and novel alternatives are needed. Here, the efficacy of acellular nanostructured fibrin-agarose hydrogel-based substitutes (NFAH) in the repair of scleral defects in rabbits was studied. For this, scleral defects of 5-mm diameter were made on 18 adult-male New Zealand rabbits and repaired with acellular NFAH, NFAH crosslinked with genipin (NFAH-GP) or glutaraldehyde (NFAH-GA), allogeneic scleral graf...
Source: Experimental Eye Research - June 29, 2019 Category: Opthalmology Authors: Carriel V, Vizcaíno-López G, Chato-Astrain J, Durand-Herrera D, Alaminos M, Campos A, Sánchez-Montesinos I, Campos F Tags: Exp Eye Res Source Type: research
Efficient determination of axon number in the optic nerve: A stereological approach.
Abstract Quantifying the number of axons in the optic nerve is of interest in many research questions. Here, we show that a stereological method allows simple, efficient, precise and unbiased determination of the total axon number in the murine optic nerve. Axons in semi-thin optic nerve cross sections from untreated eyes (n = 21) and eyes subjected to retinal damage by intravitreous NMDA injections (n = 32) or PBS controls (n = 5) were manually identified, counted and digitally labeled by hand. A stereological procedure was empirically tested with systematic combinations of different sampling methods ...
Source: Experimental Eye Research - June 26, 2019 Category: Opthalmology Authors: Koschade SE, Koch MA, Braunger BM, Tamm ER Tags: Exp Eye Res Source Type: research
A longitudinal study of retinopathy in the PEX1-Gly844Asp mouse model for mild Zellweger Spectrum Disorder.
Abstract Zellweger Spectrum Disorder (ZSD) is an autosomal recessive disease caused by mutations in any one of 13 PEX genes whose protein products are required for peroxisome assembly. Retinopathy leading to blindness is one of the major untreatable handicaps faced by patients with ZSD but is not well characterized, and the requirement for peroxisomes in retinal health is unknown. To address this, we examined the progression of retinopathy from 2 to 32 weeks of age in our murine model for the common human PEX1-p.Gly843Asp allele (PEX1-p.Gly844Asp) using electrophysiology, histology, immunohistochemistry, electron ...
Source: Experimental Eye Research - June 26, 2019 Category: Opthalmology Authors: Argyriou C, Polosa A, Cecyre B, Hsieh M, Di Pietro E, Cui W, Bouchard JF, Lachapelle P, Braverman N Tags: Exp Eye Res Source Type: research
Biochemical characterization of G64W mutant of acidic beta-crystallin 4.
Abstract Crystallins are structural proteins in the lens that last a lifetime with little turnover. Deviant in crystallins can cause rare but severe visual impairment, namely, congenital cataracts. It is reported that several mutations in the acidic β-crystallin 4 (CRYBA4) are related to congenital cataracts. However, the pathogenesis of these mutants is not well understood at molecular level. Here we evaluate the biochemical properties of wild type CRYBA4 (CRYBA4WT) and a pathogenic G64W mutant (CRYBA4G64W) including protein folding, polymerization state and protein stability. Furthermore, we explore the dif...
Source: Experimental Eye Research - June 26, 2019 Category: Opthalmology Authors: Li W, Ji Q, Wei Z, Chen YL, Zhang Z, Yin X, Aghmiuni SK, Liu M, Chen W, Shi L, Chen Q, Du X, Yu L, Cao MJ, Wang Z, Huang S, Jin T, Wang Q Tags: Exp Eye Res Source Type: research
Systemic exposure to CpG-ODN elicits low-grade inflammation in the retina.
Abstract Previous studies have reported that topical exposure to the toll-like receptor (TLR) 9 ligand CpG-ODN causes widespread ocular inflammation, including retinal microglial activation and posterior segment inflammation. Here we sought to determine the effects of systemic exposure to CpG-ODN in the retina and whether this inflammatory response was altered with Cx3cr1 deficiency or hyperglycaemia. Male non-diabetic Cx3cr1+/gfp and Cx3cr1gfp/gfp littermates (normoglycemic controls) and Cx3cr1+/gfpIns2Akitaand Cx3cr1gfp/gfpIns2Akita diabetic mice were injected intraperitoneally with 40 μg CpG-ODN. Immunoflu...
Source: Experimental Eye Research - June 23, 2019 Category: Opthalmology Authors: Kezic JM, McMenamin PG Tags: Exp Eye Res Source Type: research
Corneal injury: Clinical and molecular aspects.
Abstract Currently, over 10 million people worldwide are affected by corneal blindness. Corneal trauma and disease can cause irreversible distortions to the normal structure and physiology of the cornea often leading to corneal transplantation. However, donors are in short supply and risk of rejection is an ever-present concern. Although significant progress has been made in recent years, the wound healing cascade remains complex and not fully understood. Tissue engineering and regenerative medicine are currently at the apex of investigation in the pursuit of novel corneal therapeutics. This review uniquely integr...
Source: Experimental Eye Research - June 22, 2019 Category: Opthalmology Authors: Barrientez B, Nicholas SE, Whelchel A, Sharif R, Hjortdal J, Karamichos D Tags: Exp Eye Res Source Type: research
Investigating impacts of surface charge on intraocular distribution of intravitreal lipid nanoparticles.
Abstract In this paper, the effect of surface charge of intravitreal lipid nanoparticles (LNPs) on their intraocular accumulation and distribution was quantitatively and systematically studied. The retinal distribution of LNPs delivering model drug (siRNA) with optimal surface charge was visualized as well. LNPs and siRNA-loaded LNPs (siLNPs) were prepared with ethanol-injection method. C57BL/6 Mice with the age of 6-8 weeks were used for the animal experiments. Quantitative accumulation in the eye and respective intraocular distribution of the intravitreally injected LNPs with different surface charge were examin...
Source: Experimental Eye Research - June 22, 2019 Category: Opthalmology Authors: Huang X, Chau Y Tags: Exp Eye Res Source Type: research
Mendelian genes in primary open angle glaucoma.
Abstract Mutations in each of three genes, myocilin (MYOC), optineurin (OPTN), and TANK binding kinase 1 (TBK1), may cause primary open-angle glaucoma (POAG) that is inherited as a Mendelian trait. MYOC mutations cause 3-4% of POAG cases with IOP>21 mmHg, while mutations in OPTN, TBK1, and MYOC each cause ∼1% of POAG with IOP ≤21 mmHg, i.e. normal tension glaucoma. Identification of these disease-causing genes has provided insights into glaucoma pathogenesis. Mutations in MYOC cause a cascade of abnormalities in the trabecular meshwork including intracellular retention of MYOC protein, decreased aque...
Source: Experimental Eye Research - June 22, 2019 Category: Opthalmology Authors: Sears NC, Boese EA, Miller MA, Fingert JH Tags: Exp Eye Res Source Type: research
Quantitative profiling of tear proteome reveals down regulation of zinc alpha-2 glycoprotein in Aspergillus flavus keratitis patients.
In this study, we examined the proteome profile of tear samples from A. flavus keratitis patients at various stages of infection. The proteome was profiled using 2D PAGE and the protein levels were quantified using 2D DIGE. Alpha-1-antitrypsin, apolipoprotein, haptoglobin, lactoferrin and albumin were up regulated while cystatin SA III precursor, lacrimal lipocalin precursor, lacritin precursor and Zinc alpha-2 glycoprotein (ZAG) were down regulated in tear fluid. In the case of ZAG all proteoforms were down regulated as the disease progressed from early to late stage of infection. Western blot analysis confirmed the resul...
Source: Experimental Eye Research - June 21, 2019 Category: Opthalmology Authors: Parthiban N, Sampath NL, JeyaMaheshwari J, Prajna NV, Lalitha P, Dharmalingam K Tags: Exp Eye Res Source Type: research
Alterations in GRHL2-OVOL2-ZEB1 axis and aberrant activation of wnt signaling lead to altered gene transcription in posterior polymorphous corneal dystrophy.
Abstract Mutations associated with posterior polymorphous corneal dystrophy (PPCD) have been identified in three genes: ZEB1 (zinc-finger E-box binding homeobox 1) associated with sub-type PPCD3; OVOL2 (ovol-like zinc finger 2) associated with sub-type PPCD1; and GRHL2 (grainyhead like transcription factor 2) associated with sub-type PPCD4. Each of these genes encodes a transcription factor that regulates cell-state transitions. While the discovery of these PPCD-associated genes has greatly expanded our knowledge of the genetic basis of PPCD, the molecular mechanisms via which mutations in these genes lead to indi...
Source: Experimental Eye Research - June 21, 2019 Category: Opthalmology Authors: Chung DD, Zhang W, Jatavallabhula K, Barrington A, Jung J, Aldave AJ Tags: Exp Eye Res Source Type: research
Verification and spatial mapping of TRPV1 and TRPV4 expression in the embryonic and adult mouse lens.
Abstract The transient receptor protein vanilloid channels, TRPV1 and TRPV4, have recently been shown to be mechanosensors in the ocular lens that act to transduce physical changes in lens volume and internal hydrostatic pressure into the activation of signalling pathways in lens epithelial cells. These pathways in turn regulate ion and water transport to ensure that the optical properties of the lens remain constant. Despite the functional evidence that implicate the roles of TRPV1 and TRPV4 in the lens, their respective cellular expression patterns in the different regions of the lens has to date not been fully ...
Source: Experimental Eye Research - June 20, 2019 Category: Opthalmology Authors: Nakazawa Y, Donaldson PJ, Petrova R Tags: Exp Eye Res Source Type: research
In vivo effect of bevacizumab-loaded albumin nanoparticles in the treatment of corneal neovascularization.
na A, Irache JM Abstract Corneal neovascularization (CNV) is associated with different ocular pathologies, including infectious keratitis, trachoma or corneal trauma. Pharmacological treatments based on the topical application of anti-VEGF therapies have been shown to be effective in the treatment and prevention of CNV. The aim of this work was to evaluate the effect of bevacizumab-loaded albumin nanoparticles in a rat model of CNV. Bevacizumab-loaded nanoparticles, either "naked" (B-NP) or coated with PEG 35,000 (B-NP-PEG), were administered once a day in the eyes of animals (10 μL, 4 mg/mL every...
Source: Experimental Eye Research - June 19, 2019 Category: Opthalmology Authors: Luis de Redín I, Boiero C, Recalde S, Agüeros M, Allemandi D, Llabot JM, García-Layana A, Irache JM Tags: Exp Eye Res Source Type: research
Dynamic changes of the extracellular matrix during corneal wound healing.
tínez-García MC Abstract The extracellular matrix (ECM) confers transparency to the cornea because of the precise organization of collagen fibrils and a wide variety of proteoglycans. We monitored the corneal wound healing process after alkali burns in rabbits. We analyzed the location and expression of collagens and proteoglycans, the clinical impact, and the recovery of optical transparency. After the animals received both general and ocular topical anesthesia, the central cornea of the left eye was burned by placing an 8-mm diameter filter paper soaked in 0.5 N NaOH for 60 s. The eyes were eva...
Source: Experimental Eye Research - June 19, 2019 Category: Opthalmology Authors: Lorenzo-Martín E, Gallego-Muñoz P, Mar S, Fernández I, Cidad P, Martínez-García MC Tags: Exp Eye Res Source Type: research
Menopause exacerbates visual dysfunction in experimental glaucoma.
Abstract Glaucoma is the leading cause of irreversible blindness worldwide. Recently, estrogen deficiencies caused by early menopause, alterations in estrogen signaling via mutations in estrogen receptors, and polymorphisms along estrogen metabolic pathways have all been linked to an increased risk of developing glaucoma. Here, we examined how menopause and age impact visual function and retinal structure in an experimental model of glaucoma. Young (3-4 months) and aged (9-10 months) female Brown Norway rats were divided into pre- and post-menopausal cohorts by surgically inducing menopause via ovariectomy (OVX). ...
Source: Experimental Eye Research - June 18, 2019 Category: Opthalmology Authors: Feola AJ, Fu J, Allen R, Yang V, Campbell IC, Ottensmeyer A, Ethier CR, Pardue M Tags: Exp Eye Res Source Type: research
Is sex a biological variable in corneal wound healing?
Abstract Wound healing differs significantly in men and women in a tissue-dependent manner. Dermal wounds heal faster in women whereas mucosal wounds heal faster in men. However, the effect of sex as a variable in corneal wound healing is largely unknown. The primary objective of this study was to test whether sex is a biological variable in corneal wound healing activated by the trauma or injury using an established in vivo rabbit model with male and female New Zealand White rabbits. Corneal wounds in rabbits were produced by a single topical alkali (0.5N Sodium hydroxide) application. Serial slit-lamp, stereo bi...
Source: Experimental Eye Research - June 18, 2019 Category: Opthalmology Authors: Tripathi R, Giuliano EA, Gafen H, Gupta S, Martin LM, Sinha PR, Rodier JT, Fink MK, Hesemann NP, Chaurasia SS, Mohan RR Tags: Exp Eye Res Source Type: research
Age-related macular degeneration (AMD) mitochondria modulate epigenetic mechanisms in retinal pigment epithelial cells.
This study might advance the field of AMD research since in addition to highlighting the critical role of nuclear-mitochondrial interactions that influence epigenetic mechanisms in AMD patients, this work suggests epigenetic profiles as potential therapeutic targets for AMD. PMID: 31226340 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - June 18, 2019 Category: Opthalmology Authors: Nashine S, Nesburn AB, Kuppermann BD, Kenney MC Tags: Exp Eye Res Source Type: research
Effect of ocular hypertension on the pattern of retinal ganglion cell subtype loss in a mouse model of early-onset glaucoma.
In conclusion, through this study we characterized an experimental model of early onset glaucoma on a C57BL/6J background exhibiting key glaucoma phenotypes. In addition, we describe that RGC death has subtype-specific sensitivities and follows a specific pattern of cell death under glaucomatous conditions. PMID: 31211954 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)
Source: Experimental Eye Research - June 15, 2019 Category: Opthalmology Authors: Daniel S, Meyer KJ, Clark AF, Anderson MG, McDowell CM Tags: Exp Eye Res Source Type: research
Traditional two-dimensional mesenchymal stem cells (MSCs) are better than spheroid MSCs on promoting retinal ganglion cells survival and axon regeneration.
Abstract The loss of retinal ganglion cells (RGCs) is one of the common pathological features associated with optic nerve diseases leading to blindness. The aims of our study were to compare the neuroprotection of two forms of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) on RGCs and axon regeneration after optic nerve crush (ONC) in vivo, and to investigate the molecular mechanism. The effects of intravitreally transplanted hUCB-MSCs cultured in two-dimensional (2D-MSCs) and spheroids (3D-MSCs) were assessed by the survival of RGCs, regenerating axons, and flash visual evoked potentials (f...
Source: Experimental Eye Research - June 13, 2019 Category: Opthalmology Authors: Huang W, Wang C, Xie L, Wang X, Zhang L, Chen C, Jiang B Tags: Exp Eye Res Source Type: research
Activated protein C induces suppression and regression of choroidal neovascularization- A murine model.
Abstract Activated protein C (APC) exerts diverse cell signaling pathways which results in multiple distinct cytoprotective actions. These include anti-apoptotic and anti-inflammatory activities and stabilization of endothelial and epithelial barriers. We studied the ability of APC to inhibit the leakage and the growth of newly formed as well as pre-existing choroidal neovascularization (CNV) and examined the ability of APC to stabilize the Retinal Pigmented Epithelium (RPE). We explored the contribution of Tie2 receptor to the protective effects of APC. CNV was induced by laser photocoagulation in C57BL/6J mice. ...
Source: Experimental Eye Research - June 12, 2019 Category: Opthalmology Authors: Livnat T, Weinberger Y, Budnik I, Deitch I, Dahbash M, Sella R, Dardik R, Kenet G, Nisgav Y, Weinberger D Tags: Exp Eye Res Source Type: research
Validation of the Icare ® TONOVET plus rebound tonometer in normal rabbit eyes.
Validation of the Icare® TONOVET plus rebound tonometer in normal rabbit eyes. Exp Eye Res. 2019 Jun 12;:107698 Authors: Gloe S, Rothering A, Kiland JA, McLellan GJ Abstract To determine the accuracy and precision of the Icare® TONOVET Plus rebound tonometer for measuring intraocular pressure (IOP) in normal rabbit eyes, as well as compare it to three other commercially available tonometers: the Icare® TONOVET (TV01), Tono-Pen Vet™, and Tono-Pen AVIA Vet™. The anterior chambers of both eyes of three New Zealand White rabbits were cannulated, post-mortem. IOP was measured using ...
Source: Experimental Eye Research - June 12, 2019 Category: Opthalmology Authors: Gloe S, Rothering A, Kiland JA, McLellan GJ Tags: Exp Eye Res Source Type: research