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Retinal Disease (retinal + disease)
Kinds of Retinal Disease Selected Abstracts2256: Retinal disease masquerading posterior pole inflammationACTA OPHTHALMOLOGICA, Issue 2010M KHAIRALLAH [source] Retinal capillary basement membrane thickness in diabetic mice genetically modified at the haptoglobin locusDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2007Rachel Miller-Lotan Technion Faculty of Medicine Abstract Background Individuals with diabetes mellitus (DM) homozygous for the haptoglobin (Hp) 1 allele are at decreased risk of retinopathy as compared to DM individuals with the Hp 2 allele. We sought to recapitulate these findings in DM mice genetically modified at the Hp locus. Methods An early morphological characteristic of the microangiopathy seen in diabetic retinal disease is retinal capillary basement membrane (RCBM) thickening. RCBM thickness as assessed by electron microscopy was performed on a total of 12 eyes taken from three mice in each of the four study groups (three eyes from C57Bl/6 Hp 1 and C57Bl/6 Hp 2 mice with and without streptozotocin-induced diabetes). Results The non-parametric Kruskal,Wallis ANOVA test demonstrated that there was a highly significant difference between the four groups of mice (P < 0.0001). Mann,Whitney tests for specific pair-wise comparisons demonstrated that there was no significant difference in the RCBM thickness between Hp 1 and Hp 2 mice (p = 0.70) or between DM Hp 1 and non-DM Hp 1 mice (p = 0.42). However, induction of diabetes resulted in a marked increase in RCBM thickness in Hp 2 mice compared to non-DM Hp 2 mice (p = 0.0004) and compared to DM Hp 1 mice (p = 0.0005). Conclusions A highly significant increase in RCBM thickness was observed in DM mice with the Hp 2 genotype. These data provide important support for association studies done in humans showing an increased prevalence of diabetic retinopathy in individuals with the Hp 2 genotype. Copyright © 2006 John Wiley & Sons, Ltd. [source] The Y402H variant of complement factor H is associated with age-related macular degeneration but not with diabetic retinal disease in the Go-DARTS studyDIABETIC MEDICINE, Issue 5 2009A. S. F. Doney Abstract Aims, The Y402H variant of complement factor H (CFH) is associated with risk of age-related macular degeneration (ARMD). In common with ARMD, diabetic retinal disease also appears to involve complement activation. The aim was to investigate the impact of Y402H on both retinal pathologies in patients with Type 2 diabetes (T2DM) undergoing systematic eye screening. Methods, Patients with T2DM (n = 2350) were genotyped for the CFH Y402H variant. The association of genotype with retinal disease was determined in both retrospective and prospective models. Results, The retrospective study demonstrated that the HH genotype was associated with an age-adjusted odds ratio of 7.4 for ARMD (P = 2.9 × 10,11). In a longitudinal study in the disease-free cohort, the age-adjusted hazard ratio was 2.8 (P = 2.4 × 10,7). The life-time hazard ratio was 3.4 (P = 2.1 × 10,16). We found no association of Y402H with development of referable diabetic retinal disease. Conclusion, The ARMD-associated Y402H variant in CFH does not appear to be associated with diabetic retinal disease, although complement activation is involved in the pathoaetiology of both conditions. [source] Cell-penetrating peptide TAT-mediated delivery of acidic FGF to retina and protection against ischemia,reperfusion injury in ratsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 7 2010Yi Wang Abstract The development of non-invasive ocular drug delivery systems is of practical importance in the treatment of retinal disease. In this study, we evaluated the efficacy of transactivator of transcription protein transduction domain (TAT-PTD, TAT49,57) as a vehicle to deliver acidic FGF (aFGF) to retina in rats. TAT-conjugated aFGF-His (TAT-aFGF-His) exhibited efficient penetration into the retina following topical administration to the ocular surface. Immunochemical staining with anti-His revealed that TAT-aFGF-His proteins were readily found in the retina (mainly in the ganglion cell layer) at 30 min. and remained detectable for at least 8 hrs after administration. In contrast, His+ proteins were undetectable in the retina after topical administration of aFGF-His, indicating that aFGF-His cannot penetrate the ocular barrier. Furthermore, TAT-aFGF-His, but not aFGF-His, mediated significant protection against retinal ischemia,reperfusion (IR) injury. After IR injury, retina from TAT-aFGF-His-treated rats showed better-maintained inner retinal layer structure, reduced apoptosis of retinal ganglion cells and improved retinal function compared to those treated with aFGF-His or PBS. These results indicate that conjugation of TAT to aFGF-His can markedly improve the ability of aFGF-His to penetrate the ocular barrier without impairing its biological function. Thus, TAT49,57 provides a potential vehicle for efficient drug delivery in the treatment of retinal disease. [source] Analysis of Single Nucleotide Polymorphisms in the NOS2A Gene and Interaction with Smoking in Age-Related Macular DegenerationANNALS OF HUMAN GENETICS, Issue 3 2010Juan A. Ayala-Haedo Summary Age-related macular degeneration (AMD) is a complex degenerative retinal disease influenced by both genetic and environmental risk factors. We assessed whether single nucleotide polymorphisms (SNPs) in the NOS2A gene increase risk and modulate the effect of smoking in AMD. 998 Caucasian subjects (712 AMD cases and 286 controls) were genotyped for 17 SNPs in NOS2A. Multivariable logistic regression models containing SNP genotypes, age, sex, smoking status and genotype/smoking interaction were constructed. SNP rs8072199 was significantly associated with AMD (OR = 1.3; 95% CI : 1.02, 1.65; P= 0.035). A significant interaction with smoking was detected at rs2248814 (P= 0.037). Stratified data by genotypes demonstrated that the association between AMD and smoking was stronger in carriers of AA genotypes (OR = 35.98; 95% CI: 3.19, 405.98) than in carriers of the AG genotype (OR = 3.05; 95% CI: 1.36, 6.74) or GG genotype (OR = 2.1; 95% CI: 0.91, 4.84). The results suggest a possible synergistic interaction of AA genotype with smoking, although the result bears replication in larger samples. Our data suggests that SNPs in the NOS2A gene are associated with increased risk for AMD and might modulate the effect of smoking on AMD. [source] 2215: Animal models of herpetic retinitisACTA OPHTHALMOLOGICA, Issue 2010M LABETOULLE The 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. [source] 4224: The role of electrophysiologyACTA OPHTHALMOLOGICA, Issue 2010GE HOLDER Purpose To describe the roles of electrophysiology in patients with medically unexplained visual loss Methods Standardised full-field and pattern ERGs and VEPs; additional pattern appearance VEPs to quantify visual system resolution when necessary in patients with suspected non-organic visual loss. Results Selected cases will be used to illustrate the roles of electrophysiology. A diagnosis of non-organic visual loss is confirmed by the demonstration of normal visual system function in the presence of symptoms that suggest otherwise. Patients with optic nerve disease may have a normal fundus appearance, and not all macular dysfunction is associated with an abnormal appearance of the macula; both pattern VEP and pattern ERG are needed in such cases. Further, there are many patients with retinal disease where the fundus appearance may be normal but ERGs are abnormal. Conclusion Objective functional assessment with electrophysiology is indispensable to the diagnosis and management of patients with medically unexplained visual loss. [source] 4412: Immunohistochemistry and Western blot methodologies to evaluate neuroprotective agents in models of retinopathiesACTA OPHTHALMOLOGICA, Issue 2010K THERMOS Purpose Many retinopathies that lead to visual loss and blindness are characterized by neovascularization and neural retinal defects, such as a marked loss in retinal neurons and an increase in apoptosis. There are no therapeutic agents for the treatment of the neurodegenerative component of retinal disease. Immunohistochemistry and western blot methodologies were employed to determine retinal viability and to elucidate the putative neuroprotective properties of new therapeutic targets, in animal models of retinopathy (chemical ischemia, excitotoxicity, STZ). Methods To assay retinal viability, the following antibodies for retinal markers were employed in immunohistochemical assays: PKC (rod bipolar cells), ChAT, bNOS, TH (cholinergic-, nitric oxide synthetase-, and dopamine- containing amacrine cells, respectively), calbindin-containing horizontal, amacrine and cone bipolar cells, NFL and MAP1 (ganglion axons and cells, respectively). Antibodies against various pro-survival or pro-death molecules (western blots), as well as the TUNEL-assay, were employed to examine retinal apoptosis and neuroprotection. Results Loss of retinal marker immunoreactivity was differentially observed according to the animal model employed. The neuroprotection of specific retinal neurons by the new therapeutic targets examined (somatostatin and neurosteroids) reflect the existence of protein substrates involved in the mechanism of action of these molecules. Conclusion Immunohistochemical and western blot analysis techniques provide important information on the retinal damage induced by ischemic insults and the neuroprotection afforded by new targets of retinal therapeutics. [source] 2244: Update on genetics in inherited retinal diseaseACTA OPHTHALMOLOGICA, Issue 2010BP LEROY 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. [source] 2245: Electrodiagnosis in inherited retinal diseaseACTA OPHTHALMOLOGICA, Issue 2010GE HOLDER Purpose To describe the roles of electrophysiology in the diagnosis and counselling of patients with inherited retinal disease. Methods Electrophysiological testing performed to incorporate and extend the recommendations of the International Society for Clinical Electrophysiology of Vision. Results Using a case-based presentation, it will be shown that electrophysiological testing can objectively assess the function of the different cell types and layers within the retina of the patient with inherited retinal dysfunction, which enables accurate diagnosis and counselling when placed in clinical context. The roles of pattern and multi-focal ERG in the assessment of macular function will be discussed. The electrophysiological findings will be discussed in relation to imaging studies when appropriate. It will shown that distinctive electrophysiological findings can direct appropriate and therefore cost-effective mutational screening in patients with atypical fundus changes. Conclusion Electrophysiological testing is fundamental to the successful management of patients with inherited disorders of retinal function. [source] Protein screening in vitreous samples of patients with retinal vein occlusionACTA OPHTHALMOLOGICA, Issue 2009HT AGOSTINI Purpose The aim of the study was to identify proteins involved in the pathogenesis of retinopathy after retinal vein occlusion. In retinal vein occlusion, proteins penetrate from leaky vessels into the vitreous. Alternatively, retinal cells produce protein factors and release them into the vitreous. Methods Vitreous and plasma samples of patients with retinal vein occlusion or macular pucker / macular hole were analyzed by antibody microarrays and ELISA. Results An antibody based microarray with more than 500 target for screening vitreous samples initially was less enlightening than antibody arrays providing the possibility to quantify up to 30 proteins in an ELISA-like microassay. Standard curves of antibody microarrays are as linear as those of ELISAs. VEGF values were similar to values measured by ELISA. Conclusion In our screen, we found some candidate factors which are currently investigated for their potential of influencing retinopathy after retinal vein occlusion. The use of microarrays to identify protein factors involved in retinal disease in the vitreous will be discussed. [source] Pre-receptoral spectral absorption, healthy ageing and pre-clinical indications of retinal diseaseACTA OPHTHALMOLOGICA, Issue 2009E KONSTANTAKOPOULOU Purpose The aim of this study was to investigate how chromatic sensitivity changes as a function of age and to establish the extent to which such changes can be attributed to pre-receptoral spectral absorption of short wavelength light and/or changes in retinal mechanisms caused by ageing. Methods The absorption of blue light by the macular pigment (MP) and the crystalline lens and the subjects' sensitivity to rapid flicker were measured using the Macula Assessment Profile (MAP) test. Red-green (RG) and yellow blue (YB) chromatic detection thresholds were measured at the fovea for young and older subjects using the Colour Assessment and Diagnosis (CAD) test at 2.6, 26 and 65 cd/m2. The variables of interest included the spectral absorption of the lens, the optical density of the MP, subject's age and retinal illuminance. Results The absorption of blue light by the lens increased with age. Absorption of blue light by pre-receptoral filters did not affect RG chromatic sensitivity at any of the light levels investigated but had an effect on YB thresholds. The considerably higher colour vision thresholds of some subjects and the subsequent worsening of their chromatic sensitivity at the lower light level may reflect changes in the retina brought about by accelerated aging effects. Conclusion The effect of pre-receptoral absorption of blue light on chromatic sensitivity is small. Ageing affects the amount and spectral composition of the light reaching the photoreceptors and the processing of retinal signals. As a result, flicker sensitivity declines and colour vision deteriorates. Such effects arise mostly from changes in the retina. The MAP and CAD tests help us to detect the effects of accelerated ageing and retinal disease. [source] Inflammation in AMD pathologyACTA OPHTHALMOLOGICA, Issue 2008JZ NOWAK Age-related macular degeneration (AMD) is a progressive retinal disease that leads to substantial irreversible vision loss in elderly patients. Two clinical categories of AMD are distinguished: the "dry" atrophic form and the exudative neovascular or "wet" form. There is neither a preventive therapy nor a cure for both forms, although recent efforts succeeded in a more effective treatment of the wet AMD with PDT and anti-VEGF drugs. AMD is a multifactorial pathology which involves complex interaction of metabolic, genetic and environmental factors, with major biochemical-clinical abnormalities seen in four functionally interrelated tissues: photoreceptors, retinal pigment epithelium, Bruch's membrane and choriocapilaries. Four processes specifically contribute to the development of AMD pathology: lipofuscinogenesis (in RPE cells), drusogenesis (with drusen located between RPE and Bruch's membrane), inflammation (local) and choroidal neovascularization (in wet form). Although the role of immune system and inflammation has been implicated in AMD pathogenesis for many years, an impetus to intensify the research in this direction gave a recent discovery of polymorphisms in genes that encode for elements of the complement system, including factor H (CFH; Y402H), factor B, and complement component 2. An increased activity of the complement alternative pathway due to the lack of or insufficient control by CFH appears to contribute to AMD progression via immunologic mechanism which drives inflammatory response. An arising question is whether blockade of overactive complement system will be a therapeutic strategy safe for patients and effective to prevent or slowing down the macula-devastating and vision-threatening disease. Supported by grant no. 503-1023-1 from Medical University of Lodz. [source] The analysis of fundus autofluorescence patterns in retinal diseasesACTA OPHTHALMOLOGICA, Issue 2007P POPOVIC Purpose: Fundus autofluorescence (AF) imaging is a method that shows accumulation of lipofuscin in the retinal pigment epithelium cells in vivo. Fundus AF may be recorded in retinal diseases either by scanning laser ophthalmoscope or by fundus camera using the appropriate filter. The aim of this study was to analyze the AF pattern by both methods. Methods: 20 patients with different retinal diseases including retinitis pigmentosa, cone-rod dystrophy, Stargardt disease, Best macular dystrophy, central serous retinopathy and age-related macular degeneration were included in the study. AF images were obtained from each subject using a confocal scanning laser ophthalmosope and digital fundus camera. The distribution and amount of AF were compared by the use of both systems. Results: In all disease entities both instruments showed distinct pattern of AF typical for the disease. Areas of high intensity of AF recorded with HRA matched to areas of increased intensity of AF detected with fundus camera. The distribution of areas of low or absent AF also corresponded well in both systems. Images taken with conventional fundus camera were in general lower contrasted and therefore less sharp. This was particularly true for patients with even mild media opacity. The advantage of fundus camera was however a recording of AF of a greater field of view. Conclusions: AF imaging is a very useful noninvasive method for detecting RPE abnormalities. In clinical practice, when scanning laser ophthalmoscope for recording of AF is not available, conventional digital fundus camera can be used for screening of patients suspected to have retinal disease. Care should be taken in patients with nuclear cataract, as the AF image is influenced by the AF of the crystalline lens by a great amount. [source] An audit of genetic testing in diagnosis of inherited retinal disorders: a prerequisite for gene-specific interventionCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 7 2009Monika Pradhan MS MRCOphth Abstract Background:, There has been an exponential increase in the number of genes implicated in inherited retinal disease over the last decade, but the genetic and phenotypic heterogeneity limited mutation detection. The high cost of sequencing and long turn around times meant that gene testing was not a viable option, particularly in New Zealand. Recently, advancements including development of micro-array-based mutation analysis and non-for-profit laboratories have resulted in affordable and time-efficient testing. This has enabled genetic diagnostics to become an integral component of the work-up for inherited retinal disease. Methods:, Genetic testing for inherited retinal disorders was initiated via the Ocular Genetic Clinic in Auckland 2 years ago. A retrospective audit of genetic testing over this period was carried out. The results of these tests and outcomes are discussed. Results:, Thirty-five probands have undergone genetic testing for retinal disorders. This has included X-Linked Retinoschisis, Leber Congenital Amaurosis, Retinitis Pigmentosa, Albinism, Achromatopsia, Usher syndrome, Stargardt disease and Mitochondrial disease. Of these, 54% of tests (19/35) showed a rare variant or pathogenic mutation. Three couples have proceeded to investigate the options of prenatal diagnosis and/or pre-implantation genetic diagnosis. Conclusion:, The introduction of genetic testing, largely via disease arrays, has been highly successful at clarifying disease genotype in our cohort. It is now a timely and cost-effective investigation that should be elemental to the assessment of inherited retinal disease. Genetic testing in an opportune fashion permits genetic counselling, enables families to make reproductive choices and might allow the possibility of gene therapy interventions. [source] Quantification of dark adaptation dynamics in retinitis pigmentosa using non-linear regression analysisCLINICAL AND EXPERIMENTAL OPTOMETRY, Issue 6 2004Rokiah Omar PhD Purpose: Non-linear regression analysis was used to determine dark adaptation indices in people with retinitis pigmentosa and in control subjects. Methods: Dark adaptation data were collected for 13 people with retinitis pigmentosa and 21 controls using the Goldmann-Weekers Dark Adaptometer. Data were analysed using an exponential non-linear regression model and dark adaptation indices derived. The results were compared to age-related values. Results: The mean cone threshold of the group with RP (4.73 ± 0.19 log units) was significantly greater than that found in the control group (3.69 ± 0.12 log units). The rate of cone dark adaptation in the RP group was not significantly different from that of the control group. The a break in the RP group (6.46 ± 0.70 minutes) was delayed when compared to the control group (4.29 ± 0.21 minutes) and the rate of rod dark adaptation in the RF' group was slower (10 ± 2 per cent per minute) than that of the control group (15 ± 1 per cent per minute). Conclusions: This study has shown that a relatively simple data analysis can provide a more quantitative and intuitive description of dark adaptation rates in people with retinal disease. This technique will enable more effective use of dark adaptometry as a supplement to objective electrophysiology, when monitoring people with retinitis pigmentosa. [source] Overview of retinoid metabolism and functionDEVELOPMENTAL NEUROBIOLOGY, Issue 7 2006Rune Blomhoff Abstract Retinoids (vitamin A) are crucial for most forms of life. In chordates, they have important roles in the developing nervous system and notochord and many other embryonic structures, as well as in maintenance of epithelial surfaces, immune competence, and reproduction. The ability of all- trans retinoic acid to regulate expression of several hundred genes through binding to nuclear transcription factors is believed to mediate most of these functions. The role of all- trans retinoic may extend beyond the regulation of gene transcription because a large number of noncoding RNAs also are regulated by retinoic acid. Additionally, extra-nuclear mechanisms of action of retinoids are also being identified. In organisms ranging from prokaryotes to humans, retinal is covalently linked to G protein-coupled transmembrane receptors called opsins. These receptors function as light-driven ion pumps, mediators of phototaxis, or photosensory pigments. In vertebrates phototransduction is initiated by a photochemical reaction where opsin-bound 11- cis -retinal is isomerized to all- trans -retinal. The photosensitive receptor is restored via the retinoid visual cycle. Multiple genes encoding components of this cycle have been identified and linked to many human retinal diseases. Central aspects of vitamin A absorption, enzymatic oxidation of all- trans retinol to all- trans retinal and all- trans retinoic acid, and esterification of all- trans retinol have been clarified. Furthermore, specific binding proteins are involved in several of these enzymatic processes as well as in delivery of all- trans retinoic acid to nuclear receptors. Thus, substantial progress has been made in our understanding of retinoid metabolism and function. This insight has improved our view of retinoids as critical molecules in vision, normal embryonic development, and in control of cellular growth, differentiation, and death throughout life. © 2006 Wiley Periodicals, Inc. J Neurobiol 66: 606,630, 2006 [source] Low sensitivity of retina to AMPA-induced calcificationJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2003Noemí Andrés Abstract Glutamate is involved in most CNS neurodegenerative diseases. In particular, retinal diseases such as retinal ischemia, retinitis pigmentosa, and diabetic retinopathy are associated with an excessive synaptic concentration of this neurotransmitter. To gain more insight into retinal excitotoxicity, we carried out a dose,response study in adult rats using ,-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), a glutamate analogue. AMPA intraocular injections (between 0.27 and 10.8 nmol) caused no morphologic modification, but a 10.8 + 21 nmol double injection in a 10-day interval produced a lesion characterized by discrete neuronal loss, astroglial and microglial reactions, and calcium precipitation. Abundant calcium deposits similar to those present in rat and human brain excitotoxicity or hypoxia-ischemia neurodegeneration were detected by alizarin red staining within the retinal surface and the optic nerve. Glial reactivity, associated normally with astrocytes in the nerve fiber, was assessed in Müller cells. GABA immunoreactivity was detected not only in neuronal elements but also in Müller cells. In contrast to the high vulnerability of the brain to excitotoxin microinjection, AMPA-induced retinal neurodegeneration may provide a useful model of low central nervous system sensitivity to excitotoxicity. © 2003 Wiley-Liss, Inc. [source] Targeting of the retinal pigment epithelium (RPE) by means of a rapidly scanned continuous wave (CW) laser beamLASERS IN SURGERY AND MEDICINE, Issue 4 2003Ralf Brinkmann Abstract Background and Objectives Selective treatment of the retinal pigment epithelium (RPE) by repetitively applying green ,s-laser pulses is a new method for retinal diseases associated with a degradation of the RPE, which spares the neural retina. We investigated an alternative approach to realize repetitive ,s-laser exposure by rapidly scanning a continuous wave (CW)-laser beam across the RPE. Study Design/Materials and Methods An Ar+ laser beam (514 nm) with a diameter of 18.75 ,m was repetitively scanned across porcine RPE samples in vitro providing an irradiation time of 1.6 ,s per point on the central scan axis. RPE cell damage was investigated by means of the fluorescence viability assay Calcein-AM. Results The ED50 cell damage is 305 mJ/cm2 when applying 10 scans with a repetition rate of 500 Hz. The threshold decreases with the number of scans, a saturation was found at 135 mJ/cm2 with more than 500 exposures applied. The depth of focus in beam direction is 350 ,m, defined by an increase of the threshold radiant exposure by 20%. Conclusions Targeting of pigmented cells with high local resolution has been proved with a laser-scanning device. Looking ahead selective RPE-treatment, the adaptation of a laser-scanning device on a slit-lamp or into a modified retina angiograph seems to be an attractive alternative to the pulsed ,s laser device. Lasers Surg. Med. 32:252,264, 2003. © 2003 Wiley-Liss, Inc. [source] Retinal and Optic Nerve DiseasesARTIFICIAL ORGANS, Issue 11 2003Eyal Margalit Abstract:, A variety of disease processes can affect the retina and/or the optic nerve, including vascular or ischemic disease, inflammatory or infectious disease, and degenerative disease. These disease processes may selectively damage certain parts of the retina or optic nerve, and the specific areas that are damaged may have implications for the design of potential therapeutic visual prosthetic devices. Outer retinal diseases include age-related macular degeneration, pathologic myopia, and retinitis pigmentosa. Although the retinal photoreceptors may be lost, the inner retina is relatively well-preserved in these diseases and may be a target for retinal prosthetic devices. Inner retinal diseases include retinal vascular diseases such as diabetic retinopathy, retinal venous occlusive disease, and retinopathy of prematurity. Other retinal diseases such as ocular infections (retinitis, endophthalmitis) may affect all retinal layers. Because the inner retinal cells, including the retinal ganglion cells, may be destroyed in these diseases (inner retinal or whole retinal), prosthetic devices that stimulate the inner retina may not be effective. Common optic nerve diseases include glaucoma, optic neuritis, and ischemic optic neuropathy. Because the ganglion cell nerve fibers themselves are damaged, visual prosthetics for these diseases will need to target more distal portions of the visual pathway, such as the visual cortex. Clearly, a sound understanding of retinal and optic nerve disease pathophysiology is critical for designing and choosing the optimal visual prosthetic device. [source] 4222: Potential retinal causes: when and how to investigateACTA OPHTHALMOLOGICA, Issue 2010BP LEROY Purpose To describe the retinal conditions that need to be excluded when non-organic visual loss is suspected, and the investigations required to either confirm or exclude them. Methods A case presentation format will be used to illustrate those conditions which can be discovered using psychophysical and electrophysiological tests as well as special imaging including autofluorescence, infrared and red free imaging and spectral-domain optical coherence tomography, in patients in whom a non-organic origin for visual loss is suspected. Results Inherited retinal diseases such as Stargardt macular dystrophy, X-linked retinoschisis and cone dystrophy as well as Batten disease in their early stages all need to be excluded when visual loss is thought to be non-organic. In addition, several acquired retinal conditions such as acute acular neuroretinopathy need to be taken into account. visual field testing, ISCEV-standard full-field flash electroretinography, pattern electroretinography and visual evoked potentials and specialised imaging techniques contribute significantly to making the correct diagnosis. Conclusion Visual loss in a list of organic conditions may mimic non-organic visual loss. Functional testing as well as specialised imaging techniques are essential in differentiating true organic from non-organic visual loss. [source] 4141: Visual phenotyping at the "Institut Clinique de la Souris"ACTA OPHTHALMOLOGICA, Issue 2010MJ ROUX Purpose Visual diseases come in many flavors, with a large variety of affected tissues (eye anterior segment, retina, optic nerve, cortex ,), ages of onset, rate of progression and causal factors. In Western countries, if the majority of these diseases are now curable, millions of people are still affected by blindness or low vision, as many retinal diseases (age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, glaucoma,) still lack efficient treatments. In a facility devoted to mouse phenotyping as the Mouse Clinic Institute (MCI), it is thus of major importance to propose an efficient visual phenotyping platform, to pick up visual defects in screened mutants, to assess the beneficial effects of potential treatments or the eventual adverse effects of drugs targeting the CNS. Methods Methods: Mouse mutant lines from the Eumodic European project, as well as lines from specific academic projects, go through clinical observation (slit lamp, fundus imaging) in the context of a behavioral phenotyping pipeline, or are assessed in more details with angiography, optomotor response, electroretinography, retinal histology and/or immunohistochemistry. Results To illustrate the possibilities offered by the MCI visual phenotyping platform, we will present results obtained from various projects, as well as the validation of electroretinography protocols to follow dark adaptation and the effect of acute drug injections. Conclusion In an environment allowing for an in depth phenotyping, from behavior to biochemistry, metabolism and cardiology, the MCI visual phenotyping platform provides a comprehensive set of tests to get the most out of genetically modified mice. [source] 2451: What's new in neuroprotectionACTA OPHTHALMOLOGICA, Issue 2010L WHEELER Purpose Vision loss is a an important patient concern in glaucoma and retinal diseases. This talk will update recent findings with alpha-2 agonists and NMDA antagonists in light of recent clinical experience in neuroprotection. Alpha-2 agonists have been shown to be neuroprotective in many animal models by mechanisms thought to enhance neuronal survival. The physiological role of alpha-2 receptors is still an emerging area of research in the retina and optic nerve. Methods Recent experiments suggest that alpha-2 agonists can improve retinal performance in laboratory animals. The new methods to demonstrate this will be presented. How is this different than neuroprotection? Or is it? Results A number of ideas are being pursued to explain the observation of improved retinal performance: increased axonal transport in rats; changes in down stream receptor signalling, etc. Conclusion Understanding the mechanism(s)of action for how alpha-2 agonists affect neuroportection and retinal performance may lead to new medical therapies and the role of these receptors in the physiology and function of the eye. Commercial interest [source] 2114: AO adapted to SD-OCTACTA OPHTHALMOLOGICA, Issue 2010W DREXLER Purpose Optical coherence tomography (OCT) has emerged as a leading technique in ophthalmic imaging due to its capability to non-invasively resolve tissue morphology with high sensitivity and high axial resolution. Despite increases in axial resolution, monochromatic ocular aberrations limited the transverse resolution for retinal imaging to ~20 ,m, which is too large for visualization of cellular structures. Adaptive optics (AO) may be used to correct such aberrations, leading to an improvement in image contrast and lateral resolution. Methods A successful combination of ultra-high speed (120,000 depth scans/s), ultra-high resolution optical coherence tomography with adaptive optics and an achromatizing lens for compensation of monochromatic and longitudinal chromatic ocular aberrations, respectively, allows for non-invasive volumetric imaging in normal and pathologic human retinas at cellular resolution. Results The capability of this imaging system is demonstrated through preliminary studies by probing cellular intraretinal structures that have not been accessible so far with in vivo, non-invasive, label-free imaging techniques, including pigment epithelial cells, micro-vasculature of the choriocapillaris, single nerve fibre bundles and collagenous plates of the lamina cribrosa in the optic nerve head. In addition, the volumetric extent of cone loss in two colour-blinds can be quantified for the first time. Conclusion AO OCT might provide opportunities to enhance the understanding of retinal pathogenesis and early diagnosis of retinal diseases. Commercial interest [source] 2244: Update on genetics in inherited retinal diseaseACTA OPHTHALMOLOGICA, Issue 2010BP LEROY 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. [source] 2131: Human pluripotent stem cells provide excellent source of functional pigment epithelial cellsACTA OPHTHALMOLOGICA, Issue 2010H SKOTTMAN Purpose Defined differentiation of functional RPE cells from human embryonic (hESC) or induced pluripotent stem cells (iPSC) is a prerequisite for their use in individualised disease modelling, drug discovery and transplantation for retinal diseases. In this study we report differentiation of RPE cells from hESC and iPSC in condition enabling easy translation to clinical quality cell production. Methods Pluripotent stem cells were produced on human fibroblast feeder cells in serum-free medium. The differentiation of the cells was induced using bFGF and feeder cell removal approach under serum-free conditions. The pigmentation and RPE morphology of the cells were analysed and the expression of genes and proteins characteristics for RPE cells were studied. The in vitro functionality of the cells was analysed using ELISA measurements and phagocytosis of photoreceptor outer segments. The integrity of the generated RPE layer was analysed using transepithelial electric resistance (TEER) measurements. Results With our differentiation method, we were able to generate RPE cells with satisfying efficiency. The typical pigmented cobblestone-like morphology and expression of RPE specific markers were confirmed at gene and protein level. The differentiated cells were able to phagocytose and secreted growth factors typical for RPE cells. In addition, cells formed a well polarized epithelium with high integrity, exhibiting good TEER values. Conclusion We have developed progressive differentiation protocol for production of functional RPE cells from hESC and iPSC. The developed production method is currently translated to defined and animal component free conditions enabling clinical grade cell production. [source] Angiotensin receptors in the eyes of arterial hypertensive ratsACTA OPHTHALMOLOGICA, Issue 4 2010Anu Vaajanen Abstract. Purpose:, The aim of the present study was to determine whether the eye tissues of arterial hypertensive rats evince expression of angiotensin receptors (AT1 and AT2) as well as the novel Mas receptor, whose endogenous ligand is vasorelaxing Angiotensin (1,7) [Ang (1,7)]. Methods:, Enucleated eyes from spontaneously hypertensive rats (SHR) and double transgenic rats harbouring human renin and angiotensinogen genes (dTGR) and their normotensive controls were used. Half of the rats were pretreated orally with an Angiotensin II (Ang II) type 1 receptor blocker (ARB). The eyes were snap-frozen in isopentane at ,40° and stored at ,70° for subsequent reverse transcriptase polymerase chain reaction (RT-PCR) analysis or in vitro autoradiography. Results:, The mRNA expression of AT1a and AT 2 as well as the novel Mas receptor was detected in all rat groups, being markedly higher in the retina than in the ciliary body. dTGR had significantly more receptors than SHR, but no direct relation to blood pressure level was seen. According to the autoradiography, treatment with ARB blocked a part of AT1 receptors but had no clear effect on AT2 receptors. Conclusion:, The novel Mas receptor was found by RT-PCR in eye tissue for the first time. Its specific ligand, Ang (1,7), may be involved in the regulation of intraocular pressure , as recently demonstrated by us , and in the pathogenesis of retinal diseases as a counter-regulatory component for the vascular and proliferative actions of Ang II. The results suggest that the density of AT1 receptors in the eye is independent of the blood pressure level of the animal. [source] Evaluation of choroidal blood flow after treatment of retinal diseasesACTA OPHTHALMOLOGICA, Issue 2009C CHIQUET Purpose this review aims to summarize studies which assessed the effect of treatment on choroidal blood flow. Methods this presentation will focus on studies using the laser Doppler flowmeter for the analysis of choroidal blood flow parameters (velocity, volume and flow) before and after treatment. Therapies have been assessed in different ocular disease, such as age-related macular degeneration (laser photocoagulation therapy, photodynamic therapy, transpupillary thermotherapy, sildenafil citrate, niacin, pentoxifylline), diabetes mellitus (panretinal photocoagulation, intravenous C-peptide infusion), retinal vein occlusions (isovolemic hemodilution), macular edema (diclofenac), inflammation (corticosteroid), retinal detachment (surgery) or glaucoma (nimodipine, endothelin receptor antagonist, bimatoprost, timolol, trabeculectomy). Results this paper will give insight to the effects of laser treatment (laser photocoagulation, photodynamic therapy), surgery (scleral buckling, trabeculectomy, ocular anesthesia) or systemic drugs on the choroidal blood flow. Methodological considerations will be analyzed, such as the calculation of the sensitivity of the experiments, the comparisons of different groups with or without randomization. Conclusion laser Doppler flowmetry is a useful and a non invasive technique to study the effect of treatment on choroidal blood flow. In ocular disease, investigators should be aware of the tissue scattering changes associated with a retinal or choroidal disease and the necessity of a controlled foveal fixation. [source] Intravitreal and plasmatic levels of erythropoietin after sub-conjunctival administration in rabbitsACTA OPHTHALMOLOGICA, Issue 2009AP RESENDE Purpose Recently Erythropoietin (EPO) had been shown to have neuroprotective and neuroregenerative effects on retinal ganglion cells, apart from its erythropoietic properties, being a promissory alternative on ischemic retinal diseases. With the present study we pretend to evaluate the efficacy of subconjuntival injection for ocular EPO delivery. Methods New Zealand albino rabbits (n=6) were used. Complete ophthalmic examinations were carried out before and after the injections for 15 days. The proceedings (intravitreal punch and subconjuntival injections) were carried out under general anaesthesia. Through the subconjuntival route 100 UI of EPO diluted in 50 ,l saline solution 0,9% was administered. The opposite eyes of each animal served as controls. The vitreous and plasmatic concentration of EPO were measured using the ELISA method. Results Administration of EPO through the subconjuntival route allowed a vitreous absortion that reached the highest 24 hours after administration with 0,6 mUI/ml of EPO quantified in 100 ,l of vitreous sample. The sistemic absorption reached the highest concentration 3 hours after subconjunctival administration and 48 hours after the administration the plasmatic concentration of EPO regained physiologic values. EPO was not detected on control eyes. Conclusion All the previous studies used the systemic or intravitreal route of administration to acquire therapeutic concentrations of EPO on the retina, both difficult to use in clinical practice. In this study, the subconjuntival route proved to be a promising alternative for ocular EPO delivery. However further studies are necessary to assess the blood and intravitreal kinetics of EPO after subconjuntival administration. [source] Recent developments in retinopathy of prematurityACTA OPHTHALMOLOGICA, Issue 2009B MORTEMOUSQUE The retinopathy remains the principal severe ophthalmologic complication of neonates with a gestationalage of 32 weeks or less. It's a major cause of lifelong blindness beginning in infancy. As many other ocular pathologies, including diabetic retinopathy, and age-related macular degeneration, result in vision loss because of aberrant neoangiogenesis. A common feature of these conditions is the presenceof hypoxic areas and overexpression of the proangiogenic vascular endothelialgrowth factor (VEGF). Its prevantion can be made by a better management of the oxygenation of these children but also by a better knowledge of the other risk factors. The prevailing current treatment, laser ablation of the retina, is destructive and only partially effective. Preventive and less destructive therapies are much more desirable. So, Angiogenesis, or the formation of new retinal blood vessels is a key feature of many proliferative retinal diseases including diabetic retinopathy,retinal vein occlusions, and retinopathy of prematurity. [source] | |||||||||||||