bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging and BDNF‐deficiency upregulates heat shock protein expression in mouse retina
Authors: PURANEN J , TUULOS T , VEHANEN K , RYHÄNEN T , UUSITALO H , KAARNIRANTA K , KALESNYKAS G 
Published: December 2011

AbstractPurpose To examine heat shock protein (HSP) expression in retinas of mice that lack brain derived neurotrophic factor (BDNF+/‐) and their wild type littermates (WT) at young and old age.Methods Eyes from 2‐ and 22‐months old WT and BDNF+/‐ mice (The Jackson Laboratory, Bar Harbor, ME, USA) were used. HSP 27 kDa (HSP27), 60 kDa (HSP60) and 70 kDa (HSP70) protein levels in retina were determined by Western blotting. Paraffin‐embedded retinal sections were immunostained for HSPs to determine their localisation and abundance in various retinal layers.Results Western blot analysis of the whole retina showed a 2‐fold increase in HSP27 and HSP60, and a 1.5‐fold increase in HSP70 in aged WT mice as compared to young mice. The lack of BDNF significantly upregulated HSPs expression in retina. Thus, young BDNF+/‐ mice had similar expression levels of HSPs in retina as in old WT mice, whereas a further increase in HSPs expression was observed in aged BDNF+/‐ mice as compared to young BDNF+/‐ mice.Conclusion Aging is associated with an increased expression of HSPs in the mouse retina. The lack of BDNF induces similar expression of stress‐related proteins in retina already at young age as it is seen at old age under normal BDNF levels.
Cholesterol from diet to the retina
Authors: LECERF JM 
Published: December 2011

AbstractPlasma cholesterol is carried in the blood by lipoproteins. Lipoproteins contains lipids (free and esterified cholesterol, triglycerides, and phospholipids, and apolipoproteins). There are in the fasting condition three kinds of lipoproteins : very low‐density lipoproteins which are coming from the liver, and contain triglycerides and cholesterol ; low‐density lipoproteins which contain mainly cholesterol and apolipoprotein B, and high‐density lipoproteins which are involved in the reverse transport of cholesterol. Lipoproteins bring cholesterol to the tissues and cells which use it (gonads and adrenal glands, liver…) and triglycerides which are source of energy for muscle or are stored in adipose tissue The regulation of the plasma lipids metabolism is complex under genetic factors controlling receptors, apolipoprotein synthesis, and other proteins (for transfert, exchanges…). Dietary factors and metabolic factors such as abdominal adiposity may modulate the lipid metabolism. A lot of abnonnalities may affect the level of LDL or HDL cholesterol due to genetic defects, or nutritional diseases. The interpretation of a dyslipidemia often needs a global approach in order to identify the mechanisms, the consequences (cardiovascular risk) and the best treatment with hypolipidemic drugs and/or dietary changes.
The effects of thermal sources emitted infrared radiation (IR) on rabbit corneal and crystalline lens extracellular molecules and the influence of cyclooxygenase (COX) inhibition
Authors: ALMALIOTIS D , DADOUKIS P , KARAMPATAKIS V , KARAKIOULAKIS G , PAPACONSTANTINOU E , KOMNINOU A 
Published: December 2011

AbstractPurpose To investigate the effect of acute and chronic exposure to IR on rabbit corneal and lens metalloproteinase‐2 (MMP‐2), MMP‐9 and glycosaminoglycans (GAGs) and the influence of COX inhibition.Methods Fourteen (14) New Zealand rabbits were used totally. Chronic exposure to IR included 4 month irradiation of 3 rabbits, whereas 3 animals were the control group. Regarding acute exposure, 8 rabbits were used, diclofenac sodium eye drops 0.1% were instilled in their right eyes and 4 of them were irradiated for 12 hours. By comparing the left irradiated with the left non‐irradiated eyes, the effect of IR exposure was investigated. COX inhibition role with and without IR exposure was determined, by comparing the left with the right eyes of the irradiated and the non‐irradiated rabbits separately.The cornea and lens were extracted, followed by gelatin zymography to determine MMP‐2 and MMP‐9 activity, GAGs isolation, measurement of uronic acids and electrophoresis on cellulose acetate membranes for GAGs analysis.Results Chronic IR exposure induced the activity of corneal and lens pro‐MMP‐2 activity but did not affect GAGs. Acute exposure increased corneal and lens pro‐MMP‐2 activity and lens heparan sulfate amount, whereas the use of diclofenac sodium was unable to influence these effects.Conclusion Corneal and lens acute and chronic IR exposure induced the activity of pro‐MMP‐2. Acute exposure, also, increased lens heparan sulfate amount.
Changes in retinal neuronal connectivity in a mouse model of dominant optic atrophy
Authors: WILLIAMS P , VON RUHLAND C , MORGAN J , VOTRUBA M 
Published: December 2011

AbstractPurpose The heterozygous mutation, B6;C3‐Opa1Q285STOP which models autosomal dominant optic atrophy results in a 50% reduction in Opa1 transcript and protein in the mouse retina and neural tissues and is associated with visual dysfunction mirroring that found in human patients. We have previously reported retinal ganglion cell dendropathy in the absence of cell loss in this model. This study aims to explore the mechanisms that underlie this retinal ganglion cell dendropathy.Methods Changes in retinal ganglion cell connectivity were explored in Opa1+/‐ mutant mice (n = 27) and accompanying age and sex matched controls (wt; n = 27) at 3 time points (12, 14 and 15 months of age) by immunohistochemistry, western blot analysis, TUNEL labelling and electron microscopy.Results We report RGC dysfunction and changes in RGC connectivity in the absence of soma loss or microglial activation. We observed a dramatic decrease in PSD‐95 levels across all ages in the Opa1+/‐ mice suggesting synaptic atrophy coupled with a selective degeneration of glutamatergic but not GABA‐ergic synaptic sites. There was an increase in synaptic vesicle distribution assessed by immunohistochemistry, western blot and electron microscopy. γ‐synuclein labelling confirmed stable RGC populations without significant evidence of apoptosis on TUNEL staining.Conclusion In conclusion; we show discrete changes in RGC connectivity localised to sublamina b. These results highlight the importance of normal mitochondrial fusion balance as influenced by the OPA1 protein in maintaining neural cell connectivity. Changes in connectivity precede the onset of clinical visual loss and structural changes in optic nerve in the absence of significant apoptosis or microglial upregulation.
Pupillometric quantification of residual rod and cone activity in patients with visual loss due to Leber congenital amaurosis
Authors: KAWASAKI A , MUNIER FL , LEON L , KARDON RH 
Published: December 2011

AbstractPurpose Leber congenital amaurosis (LCA) is a group of genetically heterogeneous retinal dystrophies in which severe visual impairment occurs at infancy or during early childhood. We describe the threshold response function of rods and cones, as determined from pupil responses to colored light stimulation over a range of intensities, in 4 patients with LCA with different gene mutations who each had very poor visual function and non‐recordable ERG.Methods Four subjects with LCA and 10 control subjects underwent computerized pupillography under conditions of dark adaptation. The pupil response to a 1 second red (640 ± 10nm) and blue (467 ± 17nm) Ganzfeld light from ‐4.0 to 2.0 log cd/m2 was recorded continuously. Pupil responses to low light intensities were used to define the response curve of rods and the rod threshold for blue and red light. When rod‐related pupil responses were absent, those obtained from red light stimulation at brighter intensities could be used to estimate cone activity.Results A rod‐related pupil response curve was still preserved and defined in only one patient (RDH mutation) using blue light and the repsonse threshold was ‐3.1 log cd/m2 . This was almost 2 log‐units greater than the mean value in normal eyes (‐4.9 log cd/m2 blue light). Residual cone activity in all 4 LCA patients yielded response thresholds of ‐2.3, ‐0.9, ‐0.8 and ‐2.1 log cd/m2.Conclusion Pupillometry can estimate residual function and threshold responses of rods and cones in advanced stages of LCA. As such, pupillometry expands the dynamic range of photoreceptor activity that can be objectively monitored, either to follow natural progression or to assess effects of intervention.
Commercial interest
Beijing Eye Public Health Care Project
Authors: JONAS JB , XU L , CUI TT , YOU QS , WANG YX , YANG H , LI JJ , WEI WB , LIANG QF , WANG S , YANG XH , ZHANG L 
Published: December 2011

AbstractPurpose The Beijing Eye Public Health Care Project was designed to screen all elderly subjects (age 55‐85 years) of the rural region of Greater Beijing. It was developed as preparatory step for a telemedicine based public health care system in ophthalmology in China.Methods Project participants were visited, interviewed and examined by 2500 trained barefoot doctors. If visual acuity was <0.3, subjects were referred to primary health care centers where ocular photographs were taken. Using telemedicine, the photographs were transmitted to a reading center and causes for visual impairment were diagnosed.Results Out of 692,323 eligible inhabitants, 562,788 (81.3%) subjects participated. Visual impairment in at least one eye was detected in 54,155 (9.62%) subjects, and 30,164 (5.36%) subjects had bilateral visual impairment. Ocular fundus photographs were taken for 37,281 subjects. Cause for visual impairment was cataract in 19,163 (3.41%) of all screened subjects, glaucoma in 1,606 (0.29%) subjects, diabetic retinopathy in 905 (0.16%) subjects, other macular diseases in 2,700 (0.48%) subjects, pterygium in 1381 (0.25%) subjects, and corneal leukoma in 283 (0.05%) subjects. For 5,853 (1.04%) subjects, a diagnosis of urgent cataract surgery was made. After cataract surgery, visual acuity was ≥0.3 in 1464 (91.7%) of 1596 postoperatively re‐examined subjects.Conclusion Using a telemedicine approach, the Beijing Eye Public Health Care Project developed, applied and tested an infrastructure for ophthalmic mass screening of more than 500,000 elderly inhabitants with a response rate of >80%. Besides cataract, retinal diseases including diabetic retinopathy and glaucoma were major causes for visual impairment.
Inhibition of mitocondrial complex IV in cell death and the influence of light.
Authors: OSBORNE N 
Published: December 2011

AbstractPurpose Characterise the mechanism by which the mitochondrial complex IV poison sodium azide kills RGC‐5 cells (cell line with certain ganglion cell properties) in the dark and determine the influence of white and red light.Methods RGC‐5 cell cultures in 96‐ or 12‐well plates were exposed to different concentrations of sodium azide in the dark or under white (400‐700nm, 1000 lux) or red (625‐635nm, 1000lux) light. Cells were analysed 24‐96 hours later for production of reactive oxygen species (ROS), cell viability (MTT procedure) and for apoptosis (staining for phosphatidylserine and DNA breakdown). Also, cultures were subjected to immunocytochemistry for the localisation of certain antigens or their proteins extracted and subjected to electrophoresis and western blotting for various proteins involved in cell death.Results Sodium azide (5mM)‐induced apoptosis of RGC‐5 cells is characterised by positive membrane staining for phosphatidylserine, breakdown of DNA, a generation of ROS production, the activation of p38 MAPK and by inhibition with the caspase inhibitor z‐VAD‐fmk. Sodium azide also caused p38 MAPK to be translocated from the nucleus to the cytoplasm and the stimulation of alpha fordrin and caspase‐3 content. White light exacerbated and red light reduced the effects of sodium azide that occurred in the dark.Conclusion Red light as opposed to white light acting directly on the retina might protect neurones from dying by apoptosis where their mitochondria are affected.
MHC‐II Glial upregulation in contralateral mice retina to experimental glaucoma
Authors: GALLEGO BI , DE HOZ R , RAMIREZ AI , SALAZAR JJ , ROJAS B , TRIVINO A , VALIENTE‐SORIANO FJ , SALINAS‐NAVARRO M , RAMIREZ JM 
Published: December 2011

AbstractPurpose To analyze the effects of laser‐induced ocular hypertension (OHT) in MHC‐II expression in the glia of eyes with OHT (OHT‐eyes) and contralateral eyes two weeks after lasering.Methods Adult Swiss mice were divided into two groups: naïve (n=6) and lasered (n=6). Retinal wholemounts were immunostained with antibodies against GFAP, Iba‐1 and MHC‐II.Results In the naïve retinas, a weak constitutive MHC‐II expression was scarcely found in some Iba‐1+ cells and rarely in astrocytes. A small dendritiform subpopulation of Iba‐1+ cells, located in the juxtapapillary area and in the marginal region of the retina, had a strong MHC‐II immunoreaction. In comparison naïve results, in the contralateral eye, MHC‐II was expressed in Müller cells and was upregulated in Iba‐1+ cells as well as in the astrocytes. In contralateral macroglia, MHC‐II was preferentially expressed by astrocytes. In OHT‐eyes, Iba‐1+ cells showed MHC‐II immunoreactivity similar to contralateral and no MHC‐II astrocytes were observed; however, MHC‐II expression was upregulated in several groups of Müller cells thoroughout the retina and was preferentially located in the end‐foot of the cells.Conclusion Two weeks of laser induced‐OHT produced macro and microglial retinal changes in MHC‐II expression in both, contralateral and OHT‐eyes. Our results suggest that the gliotic behavior in contralateral untreated eyes could be related to the immune response. On the basis of the glial changes observed, the use of the contralateral eye as a control in experimental unilateral OHT should be reconsidered.
A hypothesis about structural changes of the posterior pole based on scleral deformation during ocular movements
Authors: THEOCHARIS IP 
Published: December 2011

AbstractPurpose To propose a theoretical model of the pathogenesis of various macular diseases based on structural deformation of the stratified posterior pole during ocular movementsMethods CT, MRI and OCT scans show evidence of significant deformation of the posterior sclera wall during ocular movements.The posterior pole is seen as a stratified model of multiple layers with different elastic properties.The morphology of lessions of various macular diseases is examined as a consequence of the compression of the stratified posterior pole using basic principles of mechanics.Results The clinical expression of various macular diseases such as age‐related macular degeneration, macular hole, central serous choroidopathy could be explained by a unifying mechanism of structural changes that includes the role of the choroidal bed as a dampening stroma.Conclusion The structural behavior of the multilayered stratified posterior pole during ocular movements may open a new field of research and treatment of the posterior pole diseases.
AICAR induces autophagy in ARPE‐19 cells
Authors: KAARNIRANTA K , VIIRI J , AMADIO M , HYTTINEN J , PAIMELA T , RYHÄNEN T , MARCHESI N , AKHTAR S , PASCALE A , PETROVSKI G , SALMINEN A 
Published: December 2011

AbstractPurpose The pathogenesis of age‐related macular degeneration involves impaired protein degradation in retinal pigment epithelial (RPE) cells. The ubiquitin‐proteasome pathway and the lysosomal pathway including autophagy are the major proteolytic systems in eukaryotic cells. Recently, p62/sequestosome 1 (p62) has been shown to be a key player linking the proteasomal and lysosomal clearance systems. In the present study, the effects of AICAR (AICA ribonucleotide, 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside) and MG‐132 (proteasome inhibitor) on autophagy regulation in ARPE‐19 cells were evaluated.Methods The AMP activated protein kinase (AMPK), p62 and ubiquitin protein levels were analyzed by western blotting. pDendra2‐hLC3 construct was used to detect macroautophagy in confocal microscopy analysis. Transmission electron microscopy was used to detect protein aggregates and autophagosomes. Cellular permeability was measured by analyzing lactate dehydrogenase levels in culture medium.Results MG‐132 (5 microM) triggered the accumulation of perinuclear aggregates that strongly colocalized with p62 and ubiquitin. AICAR (2mM) induced autophagy clearance of p62 and ubiquitin positive protein aggregates without increasing cellular permeability. Cellular energy status regulator AMPK or p‐AMPK levels were not significantly changed in response to AICAR treatment.Conclusion Our findings open new avenues for understanding the mechanisms of proteolytic processes and indicate that AICAR could be useful in the acceleration of protein clearance in RPE cells.
BDNF‐deficiency upregulates SIRT2 expression but does not affect cellular metabolism in mouse retina
Authors: PODRACKA L , VEHANEN K , TUULOS T , RÖNKKO S , KAARNIRANTA K , UUSITALO H , KALESNYKAS G 
Published: December 2011

AbstractPurpose Brain derived neurotrophic factor (BDNF) is essential for cell development, function and survival. Mammalian sirtuins (SIRT) are deacetylase enzymes that are known to play an important role in longevity. In the present study we aimed to compare SIRT1 and SIRT2 expression in retinas of mice that lack brain derived neurotrophic factor (BDNF+/‐) and their wild type littermates (WT) at young age in relation to cellular metabolism.Methods Eyes from 2‐months old WT and BDNF+/‐ mice (The Jackson Laboratory, Bar Harbor, ME, USA) were used. SIRT1 and SIRT2 protein levels in retina were determined by Western blotting. Paraffin‐embedded retinal sections were immunostained for SIRT1 and SIRT2 to determine their localisation and abundance in various retinal layers. Metabolic state of mouse retinal cells was assessed by measuring NAD+, NADH and total NAD levels using resazurin‐based assay.Results Western blot analysis of the whole retina showed that SIRT1 expression is similar in WT and BDNF+/‐ mice. However, there was a significant upregulation of SIRT2 protein level in BDNF+/‐ mice compared to WT littermates. Assessment of NAD+, NADH and total NAD levels showed similar cellular metabolic state in retinas of WT and BDNF+/‐ mice.Conclusion Our results indicate increased tubulin deacetylation in retinas of BDNF+/‐ mice, which is independent from cellular energy metabolism.
Effect of fixation and embedding methods on collagen fibrils diameter and spacing
Authors: AKHTAR S , ALMUBRAD T 
Published: December 2011

AbstractPurpose The corneal tissue are usually fixed in fixatives and embedded in resin for ultrastructural studies. Here we study the effect of these fixatives and resins on the collagen fibril (CF) diameter and the spacing between the fibrils.Methods Four normal human post‐mortem corneal buttons of 24, 25, 54 and 75 year old individuals were used. A part of each cornea was fixed in paraformaldehyde (4%) and embedded in LR White at 4°C under UV light for 24hrs. A second part of each cornea was fixed in glutaraldehyde (2.5%) + osmium tetroxide. The third part of each cornea was fixed in 2.5% glutaraldehyde containing cuprolinic blue in sodium acetate buffer for ultrastructural studies. The tissues were embedded in spurr resin at 70°C for 12 hrs. Ultra‐thin sections were stained with uranyle acetate and lead citrate.Results In the tissue, fixed paraformaldehyde (4%) and embedded in LR White at 4°C under UV light for 24hrs, the CF diameter was 24± 0.1nm and spacing between CF was 39±0.1nm. In the tissue fixed in glutaraldehyde (2.5%) + osmium tetroxide, and embedded in spurr resin, the diameter was 28.37 ± 5.84nm and spacing between CF was 45 ±4.57nm. In the tissue, fixed in 2.5% glutaraldehyde containing cuprolinic blue in sodium acetate buffer and embedded in spurr resin, the diameter was 33.75 ± 3.65nm and spacing between CF was 48.06 ±4.35nm.Conclusion Our study shows that there is a variation in the collagen fibril diameter and spacing depending on the method of fixation and embedding resins. This needs to be considered when comparative studies employing differ
Conjunctival antigen presenting cells: Sentinels for ocular surface inflammation
Authors: NIEDERKORN J 
Published: December 2011

AbstractPurpose To evaluate the role of conjunctival antigen presenting cells (APC) in experimental dry eye disease (EDE) and in the immune rejection of corneal allografts.Methods Ocular surface APC were depleted by subconjunctival injection of liposomes containing clodronate. APC depletion was confirmed by immunohistochemistry using anti‐CD11c (dendritic cells) and anti‐Iba1 (macrophages) antibodies. EDE was induced by exposing mice to desiccating stress (DS) for 5 days and pathogenic CD4+ T cells were to T cell‐deficient nude mice. Experiments were also performed in a murine model of keratoplasty.Results Injection of clodronate liposomes produced 65% and 86% reductions in conjunctival macrophages and DC respectively. Depletion of APC prior to DS inhibited the generation of autoreactive CD4+ T cells and prevented EDE. APC deletion in nude mice prior to their receiving EDE‐producing CD4+ T cells significantly mitigated EDE. APC depletion prior to keratoplasty completely prevented corneal allograft rejection. However, depleting APC in nude mice prior to transferring CD4+ T cells did not affect corneal allograft rejection indicating that primed CD4+ T cells do not require secondary activation by APC to mediate graft rejection.Conclusion Ocular surface APC play an important role in the generation of autoreactive pathogenic CD4+ T cells that mediate EDE and for secondary activation of these cells at sites of ocular surface inflammation. Ocular surface APC are also crucial for the induction of corneal allograft rejection, but secondary activation of previously primed allospecific CD4+ T cells by resident ocular surface APC is not required. Targeting ocular surface APC may be a facile therapeutic modality for managing ocular surface inflammation.
Radiation cataracts: epidemiology and biology
Authors: KLEIMAN N 
Published: December 2011

AbstractPurpose The lens is one of the most radiosensitive tissues in the body. Ocular ionizing radiation exposure results in characteristic, dose related, progressive changes leading to cataract formation. While initial, early stages of such opacification may not cause visual disability, the severity of such changes progressively increases with dose until vision is impaired and cataract extraction surgery may be required. The latency of such changes is inversely related to dose. Within the past few months, the ICRP released new guidelines and recommendations concerning ocular ionizing radiation exposure, significantly lowering the presumptive threshold for radiation cataract to 0.5 Gy, regardless of acute, protracted or chronic exposure. Similarly, the occupational lens exposure limit was lowered, from 150 mSv/yr to an average of 20 mSv/yr over 5 years, with no single year exceeding 50 mSv.Methods Recent human epidemiological studies have helped refine radiation cataract risk in various exposed populations. Nevertheless, considerable uncertainties remain concerning the precise pathobiology and the relationship between cataract development, age at exposure, threshold dose and genetic determinants of radiosensitivity.Results Recent findings will be reviewed and new data on the genetic and individual basis of radiation cataract risk will be presented.Conclusion New ICRP recommendations are likely to have significant implications for presumed radiation cataract risk, especially in radiosensitive individuals, as well as the need for occupational eye protection in fields such as interventional medicine. Cellular and molecular pathways leading to radiation cataract have fundamental relevance to that in other tissues and likely involves genomic damage, abberent division and abnormal differentation.