Home About us Contact
|
Home About us Contact | ||
|
|
||
Ocular Tissues (ocular + tissue)
Selected AbstractsEffects of (,)-carveol and HPMC on the in vitro ocular transport and the in vivo intraocular pressure lowering effects of dorzolamide formulations in normotensive New Zealand rabbitsDRUG DEVELOPMENT RESEARCH, Issue 3 2009Mohsen I. Afouna Abstract The objective of the current study was to maximize the ocular bioavailability of the carbonic anhydrase inhibitor, dorzolamide hydrochloride (DZD) via (a) enhancement of DZD corneal transport using terpene enhancers, (b) reducing pre-corneal loss of the installed dose via increased formulation viscosity, and (c) assessment of the in vivo intraocular pressure (IOP) lowering effects of test formulations using rabbit. DZD was formulated as a 2% ophthalmic solution containing different concentrations of HPMC as a viscosity improving agent (VIA), and (,)-carveol as a corneal penetration enhancer. The transport of DZD from test formulations was quantitatively determined using in vitro diffusion experiments, the permeability parameters were mathematically calculated, and the in vivo IOP lowering effects were assessed using a Tono-Pen XL® tonometer. The results revealed a good correlation between the in vitro permeability parameters and the in vivo ,IOP. The magnitude of the DZD-IOP lowering effects and durations of actions for DZD formulations were dependent on (a) the concentration of (,)-carveol, and (b) the contact period with ocular tissue which was found to be a single-valued function of the HPMC as VIA. Drug Dev Res 70, 2009. © 2009 Wiley-Liss, Inc. [source] Expression of GITR ligand abrogates immunosuppressive function of ocular tissue and differentially modulates inflammatory cytokines and chemokinesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2006Sankaranarayana Abstract The glucocorticoid-induced TNF-related receptor ligand (GITRL) was previously shown to be constitutively expressed at low levels in human eye, including retinal pigment epithelial (RPE) cells. By expressing enhanced yellow fluorescent protein-tagged human GITRL in human RPE cells, we investigated the significance of expression of GITRL on human ocular tissue. Confocal immunofluorescence microscopy and flow cytometry confirmed the surface expression of GITRL on RPE cells. However, a soluble form of GITRL was also detected. Remarkably, expression of GITRL on the RPE cells abrogated RPE-mediated immunosuppression of CD3+ T cells, implicated as a possible mechanism for ocular immune privilege. This abrogation of immunosuppression by GITRL-RPE was dependent on GITR-GITRL interaction and could not be mimicked by anti-CD28 antibody. Analysis of cytokine profiles revealed high level of TGF-beta during the immunosuppression by RPE cells while expression of GITRL abrogated the RPE cell-induced TGF-beta secretion. Expression of GITRL also stimulates secretion of an array of proinflammatory cytokines/chemokines from T cells. GITR-GITRL interaction provides a unique proinflammatory costimulation that may signal through a different pathway than that of CD28-B7 costimulation. This study implicated that GITRL could be a potential candidate for regulation of the ocular immune privilege and the balance between immune privilege and inflammation. [source] Non-invasive monitoring of commonly used intraocular drugs against endophthalmitis by raman spectroscopyLASERS IN SURGERY AND MEDICINE, Issue 4 2003K. Hosseini MD Abstract Purpose To develop a non-contact and non-invasive method for quantification of the local concentration of certain antibiotic and antifungal drugs in the eye. Study Design/Materials and Methods An integrated CCD-based Raman spectroscopic system designed specifically for ophthalmic applications was used to non-invasively detect the presence of ceftazidime and amphotericin B in ocular media. Specific Raman signatures of the above named drugs were determined for various concentrations that were injected through a needle in the aqueous humor of rabbit eyes in vivo. Raman spectra were subsequently acquired by focusing an argon laser beam within the anterior chamber of the eye. Results Compared to ocular tissue, unique spectral features of ceftazidime appeared near 1,028, 1,506, 1,586, and 1,641 cm,1. Amphotericin B exhibited its characteristic peaks at 1,156.5 and 1,556 cm,1. The amplitude of the spectral peak corresponding to these drugs (acquired by 1 second exposure time and 25 mW of laser power) were determined to be linearly dependent on their local concentration in the anterior chamber of the eye. Conclusions Raman spectroscopy may offer an effective tool to non-invasively assess the local concentration of the delivered drugs within the ocular media. This technique potentially could be used to investigate the pharmacokinetics of intraocular drugs in vivo either from a releasing implant or a direct injection. Lasers Surg. Med. 32:265,270, 2003. © 2003 Wiley-Liss, Inc. [source] 4145: Analysis of mouse eye mutants as models for human diseasesACTA OPHTHALMOLOGICA, Issue 2010S JADEJA Purpose The Eumodic (European Mouse Disease Clinic) project screens mouse knockout lines and ENU induced mutants for pathological phenotypes. Initially 2 of the strains identified with an eye defect by the Sanger MGP and a strain from the ENU mutagenesis screen at MRC Harwell have been selected for further investigation. Methods Following the initial primary phenotyping, pathology; histology; and immunohistochemistry was carried out on ocular tissue collected from mutant and control animals to determine defects in eye structure and development. This gave an indication to the underlying cause of the defects seen, enabling further molecular biology analysis. Results Btb/Poz Domain-containing Protein 12 (Btbd12) is a scaffold protein required for the formation of DNA repair complexes. The mouse knockout of this gene shows corneal opacity, dilated pupils and occasional microphthalmia, modelling the phenotypes seen in human diseases of defective DNA repair. The corneas of the mutant animals exhibit increased DNA damage which is likely to be the cause of the opacification. Solute Carrier Family 9 Member 8 (Slc9a8) is a Sodium/ Hydrogen exchanger and has previously been shown to play a role in ion exchange. The Slc9a8 knockout strain appears to have retinal degeneration and the males are infertile. The ENU-induced mutant Pedv128 exhibits defects in the retinal vasculature including defective vascular patterning and increased vascular leakage. Of particular interest is that this vascular phenotype is restricted to the eyes. Conclusion Investigation of mouse eye mutants can result in a better understanding of the pathology and underlying causes of human diseases. [source] Animal models for the treatment of bacterial keratitisACTA OPHTHALMOLOGICA, Issue 2009RP KOWALSKI Rabbit models of bacterial keratitis have been used to evaluate the efficacy of anti-infectives in the clinical treatment of bacterial keratitis. These models can determine: 1) ocular toxicity and tolerance of anti-infectives to ocular tissue, 2) penetration of anti-infectives into the cornea, and 3) anti-bacterial efficacy of the anti-infectives to corneal bacterial pathogens. The current presentation will cover the structure and limitations of rabbit bacterial keratitis modeling using published data. Topics will include statistical design, the choice of bacterial pathogens, and positive aspects for possible systemic anti-infective development. [source] Unraveling the genetics of exfoliation glaucomaACTA OPHTHALMOLOGICA, Issue 2008F JONASSON Purpose To give an account of our recent discovery (2007) of the association of lysyl oxidase like 1 (LOXL1) sequence variants and exfoliation glaucoma (XFG) as well as later replications in other populations. Methods We did a genome-wide association study on open angle glaucoma cases and controls using the Illumina 300 chip. This chip includes probes for 317.000 single , nucleotide polymorphisms (SNPs), that tag, as highly correlated surrogates about 80% of the 2.1 million known common SNPs in the Caucasian genome. For diagnosis of exfoliation syndrome a peripheral band or central shield of exfoliative material on the anterior lens capsule was required. Results When we had done 195 open angle glaucoma cases high genome wide significance was achieved on chromosome 15q24.1 an association later found to be confined to XFG only. This SNP (rs2165241T) was located in the first intron of the LOXL1 gene. We then added 11 correlated SNPs that are not on the Illumina chip and found that two non-synonymous variants in the first exon of LOXL1 can jointly account for all the observed association (R141L, OR 2.5; G153D, OR 20.1). Combined the variants explained 99% of the population attributable risk for exfoliation glaucoma. Conclusion These findings have now largely been confirmed in numerous American, Asian, Australian and European studies, and in all instances do these polymorphisms in the LOXL1 gene confer risk to XFG. LOXL1 is cross linking enzyme responsible for elastin polymer deposition in ocular tissue. The LOXL1 discovery is the first big hit in the search for genetic background for exfoliation glaucoma. These findings may soon influence monitoring of glaucoma suspects in the clinic targeting persons with the high risk haplotypes. [source] Regulation of bovine corneal endothelial cell cycle by transforming growth factor-,ACTA OPHTHALMOLOGICA, Issue 5 2003Yutaka Motegi Abstract. Purpose:,The transforming growth factor-, (TGF-,) family includes three multifunctional proteins, TGF-,1, TGF-,2 and TGF-,3, expressed in ocular tissue, which are involved in regulating cell differentiation, cell proliferation and other cell functions. TGF-, is present in aqueous humour and regulates corneal endothelial cells. This study explores the mechanism by which TGF-, regulates the cell cycle in cultured corneal endothelial cells. Methods:,The expression of specific receptors for the TGF-, family was investigated at the protein level by affinity cross-linking with radio-iodinated TGF-,1 and immunoprecipitation with specific antibodies to TGF-, receptors. Regulation of entry into the S-phase of the cell cycle was determined by 5-bromo-2, deoxyuridine (BrdU) incorporation into the cells. The signal transduction pathways were investigated using various blocking agents for protein kinase transducers involved in intracytoplasmic signal transduction. Results:,Cultured bovine corneal endothelial cells were confirmed to express TGF-, type 1 and type 2 receptors and endoglin. In the confluent state, TGF-,1 and TGF-,2 stimulated the cells to progress to the S-phase of the cell cycle through platelet-derived growth factor-B (PDGF-B) chain production and protein kinase C. Conclusions:,TGF-, accelerated cell cycle progression from the G0/G1 phase to the S-phase in cultured corneal endothelial cells, under our experimental conditions, through pathways involving protein kinase C. These pathways are related to the cross-talk between TGF-, and other cytokines. The conditions employed in the present experiments may be useful for investigating the complex cross-talk between various cytokines and growth factors. [source] Enhancing the Growth of Natural Eyelashes: The Mechanism of Bimatoprost-Induced Eyelash GrowthDERMATOLOGIC SURGERY, Issue 9 20102Article first published online: 2 APR 2010, JOEL L. COHEN MD BACKGROUND Many women desire prominent eyelashes. In December 2008, bimatoprost ophthalmic solution 0.03% was approved for the treatment of hypotrichosis of the eyelashes in the United States. OBJECTIVE To review eyelash physiology and the proposed mechanisms by which the topical pros-tamide product bimatoprost enhances eyelash growth. METHODS AND MATERIALS Clinical and preclinical studies pertaining to the efficacy, safety, and mechanisms of action of bimatoprost are presented. RESULTS Treatment with bimatoprost increases the percentage of eyelash follicles in anagen at any one time. This probably accounts for its ability to lengthen lashes. Bimatoprost-induced stimulation of melanogenesis appears to result in darker lashes and, at the same time, appears to increase the size of the dermal papilla and hair bulb, affecting lash thickness and fullness. Such effects, largely demonstrated in animal studies, are consistent with the results of a recent Food and Drug Administration phase III clinical trial. The favorable safety profile of bimatoprost in human subjects is probably secondary to the limited exposure of ocular tissues resulting from topical application at the base of the upper lashes. CONCLUSION By influencing the eyelash hair cycle and follicles, bimatoprost ophthalmic solution 0.03% is a safe and effective means of enhancing eyelash growth. Dr. Cohen has served as a consultant and clinical trial participant for Allergan, Inc. [source] Ocular Complication of PhotoDerm VL Therapy for Facial Port-Wine StainDERMATOLOGIC SURGERY, Issue 1 2003Florian K. P Sutter MD BACKGROUND A case of focal damage to the iris with distortion of the pupil secondary to PhotoDerm therapy in a 2-year-old boy is reported. OBJECTIVE To study ocular complication of photoDerm VL therapy for facial port-wine stain. METHODS Observatory case report. RESULTS. PhotoDerm VL therapy may damage ocular tissues. CONCLUSION Appropriate protection during the procedure is essential. [source] Selective expression of the small GTPase RhoB in the early developing mouse lensDEVELOPMENTAL DYNAMICS, Issue 3 2001Rupalatha Maddala Abstract This report describes the expression and distribution pattern of RhoB GTPase in the developing mouse lens. RhoB expression was confirmed by sequencing an reverse transcriptase-polymerase chain reaction,generated DNA fragment of RhoB. Immunohistochemical analysis of RhoB revealed expression in the lens vesicle (both anterior and posterior vesicle) at embryonic day (E) 11.5, and in the epithelium and primary fibers of the E14.5 lens. Compared with the neonatal stage (day 1), where RhoB is detected in the entire lens (epithelium, primary, and secondary fibers), expression of this protein is restricted to the epithelial and outer cortical secondary fibers in postnatal lenses (from day 7 to day18). Interestingly, in E11.5 and E14.5 lenses, RhoB is localized predominantly in the lens, but not detectable in the retina, cornea, or other ocular tissues. RhoB expression appears to be down-regulated in the postnatal lens with concomitant up-regulation in the retina and cornea, compared with earlier stages of development (eyes of E11.5, E14.5, and neonatal mice). This study reveals the selective expression of RhoB in the lens during early eye development and suggests a potential role for this small GTPase in cytoskeletal reorganization associated with lens epithelial cell elongation and differentiation. © 2001 Wiley-Liss, Inc. [source] Intraocular injection of tamoxifen-loaded nanoparticles: a new treatment of experimental autoimmune uveoretinitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004Yvonne de Kozak Abstract In this study, we tested the efficiency of an intravitreal injection of tamoxifen, a non-steroidal estrogen receptor modulator, in retinal soluble antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU). To increase the bioavailability of tamoxifen, we incorporated tamoxifen into polyethylene glycol (PEG)-coated nanoparticles (NP-PEG-TAM). The localization of the nanoparticles within the eye was investigated using fluorescent-labeled PEG-coated nanoparticles after injection into the vitreous cavity of rats with EAU. Some nanoparticles were distributed extracellularly throughout the ocular tissues, others were concentrated in resident ocular cells and in infiltrating macrophages. Whereas the injection of free tamoxifen did not alter the course of EAU, injection of NP-PEG-TAM performed 1,2,days before the expected onset of the disease in controls resulted in significant inhibition of EAU. NP-PEG-TAM injection significantly reduced EAU compared to injection of NP-PEG-TAM with 17,-estradiol (E2), suggesting that tamoxifen is acting as a partial antagonist to E2. Diminished infiltration by MHC class,II+ inflammatory cells and low expression of TNF-,, IL-1,, and RANTES mRNA were noted in eyes of NP-PEG-TAM-treated rats. Intravitreal injection of NP-PEG-TAM decreased S-Ag lymphocyte proliferation, IFN-, production by inguinal lymph node cells, and specific delayed-type hypersensitivity indicative of a reduced Th1-type response. It increased the anti-S-Ag IgG1 isotype indicating an antibody class switch to Th2 response. These data suggest that NP-PEG-TAM inhibition of EAU could result from a form of immune deviation. Tamoxifen-loaded nanoparticles may represent a new option for the treatment of experimental uveitis. [source] Regeneration, tissue injury and the immune responseJOURNAL OF ANATOMY, Issue 4 2006James W. Godwin Abstract The involvement of the immune system in the response to tissue injury has raised the possibility that it might influence tissue, organ or appendage regeneration following injury. One hypothesis that has been discussed is that inflammatory aspects may preclude the occurrence of regeneration, but there is also evidence for more positive roles of immune components. The vertebrate eye is an immunoprivileged site where inflammatory aspects are inhibited by several immunomodulatory mechanisms. In various newt species the ocular tissues such as the lens are regenerative and it has recently been shown that the response to local injury of the lens involves activation of antigen-presenting cells which traffic to the spleen and return to displace and engulf the lens, thereby inducing regeneration from the dorsal iris. The activation of thrombin from prothrombin in the dorsal iris is one aspect of the injury response that is important in the initiation of regeneration. The possible relationships between the immune response and the regenerative response are considered with respect to phylogenetic variation of regeneration in general, and lens regeneration in particular. [source] Effects of lutein and zeaxanthin on aspects of eye healthJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 1 2010Le Ma Abstract Lutein and zeaxanthin are members of the oxygenated carotenoids found particularly in egg yolks and dark-green leafy vegetables. A great deal of research has focused on their beneficial roles in eye health. The present article summarises the current literature related to the bioactivity of these carotenoids, emphasising their effects and possible mechanisms of action in relation to human eye health. Available evidence demonstrates that lutein and zeaxanthin are widely distributed in a number of body tissues and are uniquely concentrated in the retina and lens, indicating that each has a possible specific function in these two vital ocular tissues. Most of epidemiological studies and clinical trials support the notion that lutein and zeaxanthin have a potential role in the prevention and treatment of certain eye diseases such as age-related macular degeneration, cataract and retinitis pigmentosa. The biological mechanisms for the protective effects of these carotenoids may include powerful blue-light filtering activities and antioxidant properties. Although most studies point towards significant health benefits from lutein and zeaxanthin, further large-scale randomised supplementation trials are needed to define their effects on ocular function in health and disease. Copyright © 2009 Society of Chemical Industry [source] Pathogenesis of diabetic retinopathy and the renin-angiotensin systemOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 6 2003Hideharu Funatsu Abstract Despite the beneficial effects of good glycaemic control, loss of vision because of diabetic retinopathy (DR) still occurs. Recent studies have suggested that hypertension is a risk factor for the development and progression of DR and that blood pressure reduction can delay the progression of retinopathy. The renin-angiotensin system is activated by chronic hyperglycaemia, and the vitreous fluid level of angiotensin II (AII) is elevated in patients with proliferative diabetic retinopathy and diabetic macular oedema. AII increases vascular permeability and promotes neovascularization. It has been suggested that an autocrine-paracrine relationship may exist between AII and vascular endothelial growth factor in the ocular tissues. Accordingly, angiotensin-converting enzyme inhibitors or AII Type 1 (AT1) receptor blockers may be useful therapeutic agents for preventing the progression of DR. [source] Effect of Visible Light on Normal and P23H-3 Transgenic Rat Retinas: Characterization of a Novel Retinoic Acid Derivative Present in the P23H-3 RetinaPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2006Todd Duncan ABSTRACT Transgenic rats with the P23H mutation in rhodopsin exhibit increased susceptibility to light damage, compared with normal animals. It is known that light-induced retinal damage requires repetitive bleaching of rhodopsin and that photoreceptor cell loss is by apoptosis; however, the underlying molecular mechanism(s) leading to photoreceptor cell death are still unknown. Photoproducts, such as all- trans retinal or other retinoid metabolites, released by the extensive bleaching of rhodopsin could lead to activation of degenerative processes, especially in animals genetically predisposed to retinal degenerations. Using wild-type and transgenic rats carrying the P23H opsin mutation, we evaluated the effects of acute intense visible light on retinoid content, type and distribution in ocular tissues. Rats were exposed to green light (480,590 nm) for 0, 5, 10, 30 and 120 min. Following light treatment, rats were sacrificed and neural retinas were dissected free of the retinal pigment epithelium. Retinoids were extracted from retinal tissues and then subjected to HPLC and mass spectral analysis. We found that the light exposure affected relative levels of retinoids in the neural retina and retinal pigment epithelium of wild-type and P23H rat eyes similarly. In the P23H rat retina but not the wild-type rat retina, we found a retinoic acid-like compound with an absorbance maximum of 357 nm and a mass of 304 daltons. Production of this retinoic acid-like compound in transgenic rats is influenced by the age of the animals and the duration of light exposure. It is possible that this unique retinoid may be involved in the process of light-induced retinal degeneration. [source] Ocular Changes after Intravitreal Injection of Methanol, Formaldehyde, or Formate in RabbitsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2001Yoriko Hayasaka One hundred ,l of 1% methanol, 1% or 0.1% formaldehyde, or 1% formate was injected in the vitreous cavity of the right eyes of rabbits. The eyes were examined by biomicroscopy and ophthalmoscopy weekly. One month after injection, the eyes were enucleated and examined histologically. One week after treatment the animals that received 0.1% formaldehyde showed retinal vessel dilation, and the rabbits that received 1% formaldehyde showed mild posterior subcapsular cataract and retinal vessel dilation and haemorrhages. One month after treatment, the animals that received 0.1% or 1% formaldehyde developed mild posterior subcapsular cataract and retinal lesions. Animals that received 1% methanol or 1% formate showed nearly normal optical media and fundi. Histologically disorganized retina and optic nerve were seen in eyes that received 0.1% or 1% formaldehyde. Eyes that received 1% methanol or 1% formate appeared histologically normal. Our findings indicate that intravitreal injection of formaldehyde causes retinal and optic nerve damage, while methanol and formate are not or less toxic to ocular tissues. [source] 1261: Pathophysiology and classification of uveitisACTA OPHTHALMOLOGICA, Issue 2010AD DICK Purpose This talk will overview the pathophysiology of non-infectious uveitis in relation to recent SUN (standardised uveitis nomenclature) disease classification. Methods The experimental and translational human evidence of autoimmunity and activation of immunity will be discussed. In addition the talk will highlight the pathways and mechanisms of tissue damage that results in sight-threatening disease. Results Traditionally, despite active immune regulatory mechanisms operative within the ocular environment, inflammation still occurs. Activated antigen and non-antigen specific T cells are generated in uveitis. The interplay with innate immunity and in particular cells of myeloid lineage both systemically and within the local environment dictate the severity and extent of pathology we observe. Conclusion The understanding of immune responses during the uveitis open many avenues to potential novel immunotherapies that not only suppress inflammation but attempt to redress immune balance, tolerance and local homeostasis within ocular tissues. [source] 3121: Oxygen and treatment of ocular ischemic diseasesACTA OPHTHALMOLOGICA, Issue 2010E STEFANSSON Purpose In ischemia, reduced blood flow results in hypoxia. Hypoxic cells make hypoxia inducible factor (HIF), which controls many of the adaptive responses of tissue to ischemia. This includes vasodilatation, production of vascular endothelial factor (VEGF) with neovascularization and leakage, and finally apoptosis and tissue atrophy. Methods If hypoxia is improved this will reduce the production of VEGF and thereby reduce new vessel formation on one hand and vascular leakage and edeam formation on the other. Several methods are available to improve retinal hypoxia, including laser treatment, vitrectomy, vasodilatory drugs such as carbonic anhydrase inhibitors in addition to breathing oxygen. These treatment methods have been studied by many research groups with invasive polarographic electrodes and optical probes as well as noninvasive oxymetry in human patients and animal subjects. Results We will review experimental and clinical studies, which confirm that oxygen tension of the retina is increased following 1. retinal laser treatment 2. Vitrectomy 3. carbonic anhydrase inhibitors Conclusion Oxygen is the natural control of VEGF. VEGF levels in the retina and other ocular tissues are affected by oxygen levels and ischeimc diseases are currently treated with methods that affect oxygen and consequently VEGF. The addition of anti VEGF drugs to oxygen directed treatment such as laser and vitrectomy further influences the oxygen-HIF-VEGF-neovascularization/edema axis in ischemic retinopathies. [source] 2127: Ghrelin concentration in the aqueous humour and plasma in open angle glaucoma patientsACTA OPHTHALMOLOGICA, Issue 2010A KATSANOS Purpose Ghrelin is a peptide hormone that exerts metabolic and smooth muscle-relaxant effects in ocular tissues. The aim of this study was to compare aqueous humor and plasma levels of ghrelin in patients with open angle glaucoma (OAG) and controls. Methods Twenty four OAG, including 7 pseudoexfoliation (PXG) and 17 primary open-angle glaucoma (POAG) patients, and 30 controls were included. All participants were patients scheduled for cataract or glaucoma surgery. Patients with other concomitant ocular disease, previous ocular surgery or diabetes were excluded. Blood samples were collected before cataract surgery. Aqueous humor was aspirated from the anterior chamber through a paracentesis with a 27 G needle under sterile conditions. Ghrelin levels in both samples were measured quantitatively with commercially available Radioimmunoassay (RIA) kits. Results Mean±SD age was 71.0±9.3 and 69.6±6.6 years in the OAG and control groups, respectively (p=0.6). Plasma levels of ghrelin were 495.6±157.7 pg/ml in the OAG and 482.2±125.4 pg/ml in the control group, respectively (Mann-Whitney test, p=0.9). Aqueous humor levels of ghrelin were 85.5±15.4 pg/ml and 123.4 ±25.5 pg/ml in the OAG and control groups, respectively (Mann-Whitney test, p<0.01). The ratio of plasma/aqueous concentration in ghrelin was higher in the OAG versus the control group (5.82± 1.94 versus 4.00±1.04, Mann-Whitney test, p<0.01). There was no difference neither in plasma nor in aqueous humor levels of ghrelin between POAG and PXG patients (p>0.5). Conclusion Aqueous humor levels of ghrelin were significantly lower in OAG patients. This difference may manifest a role of ghrelin in the disease process or a consequence of antiglaucoma treatment. [source] Role of NO in retinal vascular diseaseACTA OPHTHALMOLOGICA, Issue 2009L SCHMETTERER Purpose Nitric oxide (NO) is a key regulator of vascular tone in all vascular beds including the eye. Hence, inhibition of NO synthase with L-arginine analogues leads to a reduction of blood flow to all ocular tissues. This enables the investigation of the role of NO in the physiology of blood flow regulation, but also abnormalities of the vascular L-arginine/NO system in ocular vascular disease. Methods A variety of studies investigating the role of NO in healthy humans but also in patients with vascular disease is summarized. Results Inhibition of NO synthase reduces retinal, choroidal and optic nerve head blood. A variety of studies also indicate that NO plays a role in the ocular vasodilator effects of numerous agonists including acetylcholine, bradykinin, carbon dioxide, histamine and insulin. In addition, NO appears to modulate the autoregulatory behavior of ocular vascular beds and is involved in retinal neurovascular coupling. In several ocular diseases such as diabetic retinopathy or open angle glaucoma abnormalities in the NO system can be observed. Conclusion NO is a major regulator of ocular blood flow in humans. The existence of different NO synthase isoforms makes it, however, difficult to therapeutically intervent via the L-arginine/NO pathway. Further studies are required to characterize the role of the NO synthase isoforms in the control of ocular blood flow in more detail and to allow for therapeutic interventions in ischemic ocular eye disease via this attractive pathway. [source] Why do we need a biomechanical approach to the ocular rigidity concept?ACTA OPHTHALMOLOGICA, Issue 2009KE KOTLIAR Ocular rigidity in ophthalmology is generally assumed to be a measurable surrogate parameter related to the biomechanical properties of the whole globe. Clinical tonometry and tonography, as well as recently developed methods to assess the ocular pulse amplitude and pulsatile ocular blood flow and measurements with the ocular response analyzer are based on the concept of ocular rigidity. Clinical concepts of ocular rigidity describe a resulting effect without considerations of possible diverse morphology and material properties of the different ocular tissues. It is commonly accepted that ocular rigidity is related to the elasticity of the sclera. Many formulations are however dependent on the internal volume of the globe, intraocular pressure, corneal biomechanics and thickness of the corneoscleral shell. Sometimes this is extended to biomechanical properties of the ocular vasculature and perfusion pressure. Therefore ocular rigidity is expressed in various units and has different physical meanings but the same name is used which is confusing. Ocular biomechanics introduces parameters of elasticity and viscoelasticity of the sclera, cornea and other tissues which consider the morphology of the different tissues describing their mechanical properties such as: Young's modules of the sclera and Poisson's ratios of the cornea. When applying these rigorous statements and methods of biomechanical modeling a unified concept for ocular rigidity can be developed in order to link the limited clinical concepts, to improve them and to better understand the results of clinical measurements. [source] Evidence for altered ocular rigidity in glaucomaACTA OPHTHALMOLOGICA, Issue 2009L SCHMETTERER Purpose Based on theoretical models and animal studies altered biomechanical properties of the optic nerve head and the sclera have been implicated in the pathophysiology of glaucoma. Only few data have, however, demonstrated such biomechanical alterations in vivo. We tested the hypothesis that patients with primary open angle glaucoma (POAG) have an abnormal structural stiffness based on measurements of intraocular pressure amplitude and ocular fundus pulsation amplitude. Methods Seventy patients with POAG and 70 healthy control subjects matched for age, gender, intraocular pressure and systemic blood pressure were included in this study. The ocular pulse amplitude (PA) was assessed with pneumotonometry. The fundus pulsation amplitude (FPA) was measured using laser interferometry. Based on the Friedenwald equation a coefficient of structural stiffness (E1) was calculated relating PA to FPA. Results Systemic blood pressure, intraocular pressure, and ocular perfusion pressure was comparable between glaucoma patients and healthy control subjects. FPA as well as PA was lower in patients with glaucoma than in healthy controls. The calculated factor E1 was significantly higher in patients with POAG (0.0454 ± 0.0085 a.u.) than in healthy control subjects (0.0427 ± 0.0058 a.u., p = 0.03). Conclusion This study is indicative of increased structural stiffness of the sclera in patients with POAG. This is in agreement with a number of previous animal experiments and supports the idea that the biomechanical properties of ocular tissues play a role in the process of glaucomatous ONH damage. [source] Complement factor H and factor B expression in RPE cellsACTA OPHTHALMOLOGICA, Issue 2008Purpose Age-related macular degeneration (AMD) is the leading cause of untreatable blindness in the developed world. The pathogenesis of AMD is not fully understood. Recent evidence suggests that local inflammation in particular complement activation plays an important role. We aim to understand how complement activation is regulated at retina/choroidal interface. Methods The expression and distribution of complement factor H (CFH) and factor B (CFB) in mouse ocular tissues were examined by immunohistochemistry. Regulation of CFH and CFB gene expression by various cytokines or photoreceptor outer segments (POS) was investigated in vitro in cultured RPE cells. Changes in CFH or CFB gene expression after treatment were evaluated by RT-PCR. Results In normal mouse eyes, CFH was detected in corneal epithelial cells, ciliary body, RPE cells, Bruch's membrane and choroidal vessels. There is no significant change in either the expression level or the distribution pattern of CFH in ocular tissues of different ages of mice. CFB was exclusively detected in RPE cells in normal mice. The expression of CFB in RPE cells increases with age. In vitro in RPE cultures, the expression of CFH was negatively regulated by cytokine TNF-alpha and IL-6, whereas the expression of CFB was positively regulated by TNF-alpha and IFN-gamma. Short-term incubation of RPE cells with POS did not alter the expression of CFH or CFB, whereas long-term incubation of RPE cells with POS significantly down-regulated CFH expression but up-regulated CFB expression. Conclusion Complement regulatory factors CFH and CFB are produced locally in the retina/choroidal interface by RPE cells. The production of CFH and CFB in RPE cells is regulated differently by various cytokines and oxidized POS. [source] | |||||||||||||