bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Hsp90 and HDAC inhibition and tubulin acetylation on perinuclear protein aggregation in human retinal pigment epithelial cells
Authors: KAARNIRANTA K , RYHÄNEN T , VIIRI J , HYTTINEN J , UUSITALO H , SALMINEN A 
Published: November 2010

Abstract Purpose Retinal pigment epithelial (RPE) cells are continually exposed to oxidative stress that contributes to protein misfolding, aggregation and functional abnormalities during aging. The protein aggregates formed at the cell periphery are delivered along the microtubulus network by dynein dependent retrograde trafficking to a juxtanuclear location. Methods Cellular organelles were analysed by transmission electron microscopy of ARPE‐19 cells exposed 5 µM MG‐132, 0.25 µM geldanamycin (GA), 1 µM trichostatin A (TSA), 1 µM taxol (TAX) or 5 µM nocodazole (NOC) for 24 hours. In addition, the cells were treated simultaneously with GA or TSA or TAX or NOC and MG‐132 up to 24 hours. Ubiquitin, Hsp90, Hsp70, acetylated tubulin and Hsc70 protein levels were analyzed by western blotting. Results Hsp90 inhibition by geldanamycin can effectively suppress proteasome inhibitor, MG‐132 –induced protein aggregation in a way that is an independent of HDAC inhibition, or the tubulin acetylation levels in ARPE‐19 cells. However, the tubulin acetylation and polymerization state affects the localization of the proteasome‐inhibitor –induced aggregation. Conclusion Hsp90 inhibition is effectively related to regulation of protein aggregation that is independent of HDAC inhibition or tubulin acetylation levels in the RPE cells. Our findings open new perspectives for understanding the pathogenesis of protein aggregation in retinal cells and can be useful for the development of therapeutic treatments to prevent retinal cell deterioration.
Descemet´s membrane detachment 16 years after PK and 10 months after phaco
Authors: FERNANDEZ MENDY JO , ARASANZ F 
Published: November 2010

Abstract Purpose The purpose of this paper is to present an unusual case of DMD and analyze this complication Methods A 57‐year‐old woman, who had bilateral keratoconus, underwent three penetrating keratoplasties (PK) on her RE in 1981, 1993 and 1995 resulting in ptisis bulbi. In her LE she underwent two PK (1981, 1994) follow by arcuate incisions (1995) and an uneventful phacoemulsification in 2007. 10 months after cataract surgery, she begun with blurred vision, the BCVA was 20/400 and was seen by 3 ophthalmologists who made the diagnosis of endothelial failure and suggested a new PK or a DSAEK. We performed an Optical Coherence Tomography, diagnosing a complete Descemet´s membrane detachment (DMD). An intracameral gas injection of C3F8 at 16% was performed in the operating room, and the patient was instructed to maintain a supine position. After 24 hours VA improved to 20/80 and after 72 hours 20/30 UCVA. A small bubble was present in the anterior chamber for more than 3 weeks. One month later she achieved 20/20 with Contact Lens. During the first year after reattachment it was necessary to change the CL due to an increasing with the rule astigmatism from 3D to 5D. Results Two years after gas injection BSVA is 20/25 because she is no longer using CL, Descemet´s membrane still remains well attached, even thought we realized that there was a trend to steepen the vertical meridian due to the widening of a nasal arcuate incision, that we think was the origin of the DMD. Conclusion DMD is a rare complication of Phacoemulsification, seen immediately after the surgery. So far there has not reported any complete DMD after phaco after PK. We think that it is mandatory to perform a corneal OCT in all cases of PK and stromal edema; it could probably be a DMD.
Intracorneal lenses for the treatment of presbyopia using femtosecond laser: visual outcomes and safety
Authors: PALLIKARIS IG , LIMNOPOULOU A , KYMIONIS G , PANAGOPOULOU S , BOUZOUKIS D 
Published: November 2010

Abstract Purpose To investigate the visual outcomes and safety of Intracorneal lenses (Flexivue Micro‐Lens, Presbia, CA)) for the treatment of presbyopia. Methods This was a prospective clinical study. An intrastromal corneal tunnel was created using femtosecond laser (Intralase 150, AMO , CA). The lens was inserted within the cornea tunnel of the non‐dominant eye of 10 presbiopian patients. Mean age was 51,23 years old ± 3,11 (5 males and 5 females). The follow‐up was up to 12 months. Results In the operated eye, mean uncorrected visual acuity for distance (UVA‐D) preoperatively, one day, one week one month, three months and six months, and 1 year after surgery was 20/20, 20/40, 20/40, 20/32, 20/32, 20/32 and 20/32 respectively, whereas for near (UVA‐N) was 20/50, 20/40, 20/30, 20/30, 20/25, 20/25 and 20/30. Binocular far vision was not altered. No tissue alterations of the cornea were found using corneal confocal microscopy. No intra or post‐operative complications were demonstrated up to one year after surgery. Conclusion Intracorneal lenses for the correction of presbyopia using femtosecond laser seems to be a safe and effective method to correct presbyopia in patients aged between 45 to 55 years old; a target group which is considered too old for refractive laser surgery and too young for clear lens extraction. Longer follow‐up and a larger population are necessary in order to draw more significant results of this new surgical approach for the treatment of presbyopia.
Commercial interest
Can we treat glaucoma by non‐IOP related approaches?
Authors: STALMANS I 
Published: November 2010

AbstractIntra‐ocular pressure is the main risk factor for the progression of glaucoma. However, intra‐ocular pressure lowering is not always sufficient to halt the progressive ganglion cell loss. Indeed, additional risk factors have been identified for glaucoma progression that can explain why some patients progress despite rigourous intra‐ocular pressure lowering. Vascular risk factors, such as low perfusion pressure, can be taken into account in the management of our glaucoma patients. The treatment options for these vascular risk factors will be discussed during the lecture. Moreover, neuroprotective strategies might open therapeutic perspectives to directly support the ganglion cells and thus help stabilizing the disease. Possible neuroprotective agents will be highlighted.
Are all glaucoma drugs equally effective?
Authors: SCHMETTERER L 
Published: November 2010

Abstract Purpose It is only in the recent years that we have got evidence that reducing intraocular pressure (IOP) is beneficial in terms of preventing glaucoma progression in all types of glaucomatous disease. Nowadays we do have numerous data from large clinical outcomes trials clearly indicating that the lower the IOP the better the visual field preservation. There is, however, less data available comparing outcomes of different pharmacological regimen. Methods Only few head‐to‐head comparisons of two drugs that are equally effective in lowering IOP have been published. It is generally assumed that such trials would yield similar results in visual field preservation with both regimen. Looking into the literature there is, however, some evidence for the opposite. Results One clinical trial indicates that betaxolol may be superior to timolol in terms of visual field perservation. Another trial indicates that a combination of dorzolamide and timolol is assocaited with less visual field detoriation than a combination of brinzolamide and timolol. In this study the risk of disease progression was closely linked to low blood velocities in retrobulbar vessels. Conclusion In light of these results and the lessons we have learned from other fields there is a need for further studies comparing the outcomes of different antiglaucoma drugs head‐to‐head. Given that the pathophysiology of glaucoma is only poorly understood it can not generally be expected that all glaucoma drugs are equally effective in perserving visual fields.
Commercial interest
New aspects of the Slug Mucosal Irritation (SMI) assay: Detecting ocular stinging, itching and burning sensations
Authors: LENOIR J , ADRIAENS E , CLAERHOUT I , KESTELYN P , REMON JP 
Published: November 2010

Abstract Purpose Our eyes are one of the most important senses. They are very sensitive and irritations may occur easily. A screening method for ocular discomfort would be very helpful in the development and refinement of formulations. In the past, the Slug Mucosal Irritation (SMI) assay demonstrated a relation between an increased mucus production (MP) in slugs and an elevated incidence of stinging, itching and burning (SIB) in human eyes. The aim of this study is to compare subjective ocular discomfort caused by shampoos evaluated in volunteers with results of the SIB‐procedure. Methods The stinging potency of 1 artificial tear and 10 shampoos was evaluated with the SIB‐procedure by placing 3 slugs per treatment group 3 times on 100 µl of the test item. After each 15 min contact period, MP was measured. Evaluation of the results is based upon the total MP during 3 repeated contact periods. Experiments were repeated 3 times. A Human Eye Irritation test with the same test items will be set up (12‐period cross‐over study, 24 volunteers, study approved by an independent Commission for Medical Ethics, associated with Ghent University Hospital). The participants are dripped 10 µl of a 5% or 10% shampoo dilution in water or the artificial tear in 1 eye, while in the other eye 10 µl of water is administered. The evaluation of the test substances is done both by participants and the ophthalmologist at several time points. Conclusion With the obtained results we will be able to improve the newly developed protocol and examine the predictability with reference to non‐ and mildly irritating formulations in humans. We hope to conclude that the SIB‐procedure is a good tool to predict clinical ocular discomfort.
Microplasmin as an antiscarring agent for glaucoma surgery: translation into clinical application
Authors: VANDEWALLE E 
Published: November 2010

Abstract Purpose Previously Microplasmin was investigated in a rabbit model for trabeculectomy. The combination of intracameral injections and topical drops of Microplasmin improved surgical outcome. The aqueous solution of Microplasmin used, was not optimized for use as drops or injections. Microplasmin is an autocatalytic enzyme which has a short half life when it is brought in conditions of 37°C and physiological pH. Therefore there is need for a more stable and longer acting formulation. Methods Firstly we will do pharmacological experiments to determine the rheological characterization of drug carriers with Carrier‐med rheometer. Then we will define the purity of Microplasmin bulk drug substance by RP‐HPLC. Finally, we will check the Microplasmin activity in the new obtained solutions by spectrophotometer. Secondly we will perform trabeculectomy in a rabbit model and administer the most qualified and optimized formulations. Postoperative clinical evaluation of IOP, bleb area, conjunctival vascularity and anterior chamber assessment will be performed. The eyes will be immunohistological investigated for collagen and inflammation. Conclusion Our previous data learned that the combination therapy of Microplasmin improved surgical outcome in a rabbit model, despite the fact that the formulation of Microplasmin was not optimized for use as drops or injections. Our proposed research project will optimize the formulation of Microplasmin for extended drug delivery and determine the optimal administration route and regimen. We believe that this project will allow us to further improve the positive animal data, translate this novel antifibrotic adjunctive therapy into clinical application, and thus improve the outcome after trabeculectomy in patients.
Clinical applications of corneal Scheimpflug densitometry in DSAEK and cornea guttata patients
Authors: WEYNS M , ROZEMA J , KOPPEN C , TASSIGNON MJ 
Published: November 2010

Abstract Purpose The aim of this project is to study clinical applications of corneal Scheimpflug densitometry. In the first part of the study a correlation between corneal Scheimpflug densitometry and endothelial cell count in cornea guttata will be studied. The second part will investigate a possible correlation between the smoothness of the corneal graft and postoperative visual acuity in DSAEK patients. Methods Cross‐sections of corneal Scheimpflug images will be analyzed by means of custom written software. Parameters such as average densitometry profile, position and intensity of the Bowman membrane and corneal endothelium peaks, as well as the position and intensity of the interface between an acceptor cornea and the DSAEK graft (if present) will be calculated. Results The method to analyze the corneal densitometry has already been developed and tested on corneas of contact lens wearers and post refractive surgery patients. A small number of DSAEK en cornea guttata eyes have been analyzed as well, demonstrating the potential of this technique in these patients. Conclusion Corneal Scheimpflug densitometry may be complementary to endothelial cell count in monitoring the disease progression in cornea guttata patients. Corneal Scheimpflug images may also be considered a predictor for visual outcome after DSAEK if the postoperative visual acuity variations in DSAEK patients can be linked to wrinkles in the posterior surface of the graft.
Herpetic keratitis: Herpes simplex virus versus host
Authors: VERJANS G 
Published: November 2010

AbstractHerpes simplex virus type 1 (HSV‐1) is an endemic virus worldwide that causes ocular disease in a limited but significant number of infected persons. Corneal HSV‐1 infection is clinically classified into herpetic epithelial keratitis (HEK) and herpetic stromal keratitis (HSK). HEK is an acute inflammation and results from viral toxicity of infected corneal epithelial cells. In contrast, HSK is characterized as a chronic immunopathogenic disease in which tissue injury and eventually blindness is due to the complex interplay between cells of the innate and adoptive immune response to viral antigens expressed in the corneal tissue. Studies performed on the experimental HSK mouse model greatly improved our understanding of the pathogenesis of HSK. This talk will recapitulate current insights on the virus‐host interactions involved in the initiation and perpetuation of herpetic keratitis in mice and men.
Animal models of herpetic retinitis
Authors: LABETOULLE M 
Published: November 2010

AbstractThe Herpes simplex virus (HSV) is characterized its ability to replicate in the nervous system, before inducing a latent infection with potential reactivation. Most frequent ocular complications of recurrent HSV infection are keratitis and conjunctivitis. Less frequently, the iris and the ciliary body may also be involved (anterior uveitis). The most severe HSV ocular infection is retinitis, a rare but potentially blinding disease, due to frequent bilateral involvement. Studies on human post‐mortem tissues showed that HSV is widely distributed in the population, with a preferential location within the trigeminal ganglions (innervating the cornea), but also in the superior cervical ganglions (innervating the iris) or in brain/medullar tissues (innervating the retina). Animal models have been developed to understand the pathogenic processes that lead to this rare but devastating retinal disease. Since human is the only natural host of HSV, it is difficult to obtain a perfect animal model that perfectly mimics the disease. Several animal models, based on different inoculation procedures, are thus necessary to circumscribe the anatomical, cellular and molecular aspects that lead to retinal infection. Finally, HSV retinitis appears as a clinical condition that is highly constrained by the relationships between the strain of the virus and the immune response of the host.
Endoplasmic reticulum stress and inflammation signaling in RPE cells
Authors: SALMINEN A 
Published: November 2010

AbstractPathogenesis of AMD is linked to augmentation of cellular stress, e.g. oxidative and proteotoxic stress, hypoxia and inflammation. All these conditions trigger stress in endoplasmic reticulum (ER) and in that way can disturb the protein quality control in retinal pigment epithelial (RPE) cells. ER stress stimulates the unfolded protein response (UPR) via the activation of IRE1, PERK and ATF6 transducers. The UPR signaling can restore cellular homeostasis but chronic and overwhelming stress can induce inflammatory response via different UPR signaling pathways and lead to apoptotic cell death. Moreover, ER stress is a well‐known inducer of vascular endothelial growth factor (VEGF) expression and in AMD, ER stress could provoke neovascularization and the conversion of dry form to wet counterpart. ER stress has a fundamental role in the pathogenesis of several diseases, e.g. in diabetes and neurodegenerative diseases. This lecture will review the recent advance in understanding the inducers of ER stress, present in RPE cells during AMD, and the possible role of ER stress in evoking inflammation and neovascularization during the pathogenesis of AMD.
Update on genetics in inherited retinal disease
Authors: LEROY BP 
Published: November 2010

Abstract Purpose To provide an overview of the recent developments in genetics of inherited retinal dystrophies and dysfunctions. Methods A systematic approach, supported by case presentations, will be used to illustrate an overview of new insights into genotypes and phenotypes of generalised dystrophies and dysfunctions of the retina. Results Much progress has been made in recent years in unravelling the molecular mechanisms underlying generalised retinal dystrophies and dysfunctions, with a wide variety of functions attributed to proteins encoded by causative genes. Identification of new genes such as PDE6C in achromatopsia and TRPM1 in autosomal recessive cCSNB provide further insight in retinal function. In addition, proven and confirmed success of gene therapy for Leber congenital amaurosis in man is leading the way for further treatment trials in humans suffering from different inherited retinal diseases. Conclusion Rapid progress is being made in the field of genetic retinal disease, with novel developments both in genotyping and improved detailed phenotyping. In addition, gene therapy is becoming a potentially feasible treatment option for several inherited retinal conditions.
Study of the role of P2Y receptors in the development of experimental autoimmune uveitis
Authors: JUDICE DE MENEZES RELVAS L 
Published: November 2010

Abstract Purpose During autoimmune uveitis (AU), retinal specific auto‐reactive T lymphocytes (TL) are activated, alter blood retinal barrier(BRB) and penetrate the eye where they start an inflammatory reaction. Nucleotides, normally present at low concentration in extracellular media, can act as a danger signal, through P2 receptors activation and might be implicated in AU. In this work we would like to investigate if the expression of the nucleotide receptor P2Y2 has any role in experimental autoimmune uveitis (EAU). Methods EAU will be induced in WT and P2Y2 KO mice by IRBP peptide 1‐20 injection. 12 days later, TL from spleen and lymph nodes will be purified and restimulated by IRBP. TL proliferation will be measured by thymidine incorporation and cytokines secretion by ELISA. TL from the 2 groups of mice will also be adoptively transfered in WT mice. Similarly, TL from WT mice will be adoptively transfered in WT and P2Y2 KO mice. EAU development will be graded by clinical and histological scores. Results TL generated in KO mice proliferate and produce less IFNγ and IL‐17, after IRBP restimulation than TL generated in WT mice. Accordingly, adoptive transfer of TL generated in KO mice induce significantly a lower grade of disease than those generated in WT mice. Finally, adoptive transfer of TL generated in WT mice induce disease of significantly lower grade in KO mice recipient than in WT mice recipient. Conclusion Our preliminary data shows that P2Y2 KO mice have a defective immune response after immunisation and develop lower intraocular inflammation following adoptive transfer with TL. Altogether this suggests that P2Y2, as danger receptor signals, play an important role in the development of uveitis.
Safety evaluation of intravitreal use of a beta2‐agonist in rabbit eyes
Authors: VAN CALSTER J , VERSTRAETEN S , VAN GINDERDEUREN R , STALMANS I , STALMANS P 
Published: November 2010

Abstract Purpose There is no known information on the use and safety of a long‐acting beta‐agonist, such as Clenbuterol when administered by intravitreal injection. Therefore, it is appropriate to perform this intravitreal injection in an animal model prior to start with a human experiment. The aim is to investigate the safety of an intravitreal injection of the beta2‐agonist Clenbuterol in rabbit eyes. This study is in preparation of using of this molecule in human eyes. That trial will be a monocentric, academic (investigator driven) trial to investigate the safety and efficacy of an intravitreal beta2‐agonist in patients with persistent subfoveal fluid after retinal detachment surgery. Approval of the ethics committee for the human trial has already been obtained, pending a re‐evaluation after the results of the animal study will be known. Methods An intravitreal injection of 0,1 ml solution containing 0.08µg Clenbuterol or 0.1ml NaCl 0.9% was given in 10 eyes of 10 rabbits. The distribution occurred at random and was masked. A masked investigator examined both eyes after 1, 3 and 7 days (biomicroscopy, intraocular pression and ophthalmoscopy). After one week, the rabbits were sacrificed, the eyes enucleated and fixated for histopathological examination and electron microscopy by a masked investigator. Cell death was monitored by a DNase type I/II activity assay. Results There was no clinical or histopathological difference between the clenbuterol and the control group. Conclusion Clenbuterol is not toxic for the retina of rabbit eyes after intravitreal injection. It can be considered for the use in human eyes. Final approval of the ethics committee for the human trial is awaited.
Role of VEGF‐isoforms in pathological choroidal angiogenesis
Authors: VAN DE VEIRE S , VAN BERGEN T 
Published: November 2010

Abstract Purpose The aim of this project is to study the specific role of the VEGF‐isoforms in pathological angiogenesis, and to investigate the effect of blocking a single isoform on the formation of choroidal neovascularization (CNV). Methods Endothelial and fibroblast cell cultures were made; VEGF 12, 164 or 189 was added to study their effects. VEGF‐isoform specific mice (VEGF 120/+, VEGF 164/164 and VEGF188/188 mice) , as well as double transgenic mice (VEGF 120/164, VEGF 164/188 and VEGF120/188 mice) are used to study the role of VEGF‐isoforms in pathological angiogenesis. At first, these VEGF‐isoform specific mice were backcrossed to a C75Bl/6 background. CNV was induced by placing 3 laser spots at the 9, 12 and 3 o’clock position (100µm spot size, 0.05 s spot duration and 400mW power). Quantification of the area of newly formed blood vessels was determined by retrobulbar dextran linked FITC perfusion. Results Preliminary data in endothelial cell and fibroblast cultures in vitro show that the VEGF121 and VEGF165 isoforms significantly the amount of angiogenesis, whereas the VEGF121 and VEGF189 isoforms play a role in fibrosis. In vivo, the same effects were checked on a fluorescent CD31 and Vimentin immunostaining of the choroids. An inhibition in neovascularization was present in all 3 isoform specific mice, but the effects were comparable. For the moment, mice colonies are being enlarged to repeat experiments and subsequently, these mice are intercrossed to obtain double transgenic mice. Conclusion This study will shed new light on the different role and the inhibition of the VEGF‐isoforms in CNV formation during AMD. Thus, our project may open new perspectives for the treatment of various retinopathies that are known to be associated with VEGF upregulation.