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| April 2007 | Inside IOVS | Volume 48/4 |
Epithelial-Mesenchymal Transition in the Pathogenesis of Pterygium
Pterygium is a fibrovascular disease that invades the peripheral cornea, causing visual disturbance in advanced cases. Kato et. al. (p. 1511) found that pterygial epithelial cells (PECs) showed signs of epithelial-mesenchymal transition (EMT). Intercellular adhesion was disrupted in these cells that also expressed cytokeratin 14, vimentin, and a-smooth muscle actin. Characteristic EMT changes such as downregulation of E-cadherin and intranuclear accumulation of b-catenin were also observed. Snail and Slug were also found in the nuclei of PECs but not in normal corneal epithelial cells. These results indicate that EMT by basal PECs plays a key role in the pathogenesis of pterygium.
Adenosine Prevents Thrombin Inhibition of Intercellular Communication in Cornea
Adenosine is known to prevent thrombin-induced breakdown of the barrier integrity in corneal endothelial cells. The study of D'hondt et al. (p. 1518) demonstrates that pretreatment of bovine corneal endothelial cells with adenosine prevented the inhibitory effect of thrombin on intercellular communication. The effect was mediated via A2B receptors, enhanced cAMP and Rho kinase activity, which results in decreased myosin light chain phosphorylation. Adenosine exerts its effect on gap junctional conductance as well as on paracrine intercellular communication via hemichannel-mediated release of ATP. These effects could be beneficial in overcoming the potential threat to intercellular communication in situations of inflammatory stress.
Neurofluorescent Mice: A New Model for Corneal Nerve Research
Yu and Rosenblatt (p. 1535) visualized corneal nerves in living mice as well as fixed tissue using a transgenic mouse model expressing yellow fluorescent protein (YFP) under the control of a neuron-specific promoter. The intricate patterning of the mouse corneal nerves, as well as the regeneration of injured nerves in vivo, was characterized. The ability to follow regeneration of nerves in a highly innervated and easily visualized living tissue such as the cornea provides a novel model for investigation of nerve repair.
Antioxidants May Prevent Glaucoma
Mutations in the coding region of the OPTN gene are associated with certain glaucomas. While the function of the optineurin protein is yet to be elucidated, the most common mutation, called E50K, is associated with a severe phenotype. Chalasani et al (p. 1607) show that the E50K mutation of optineurin has acquired the ability to induce cell death selectively in retinal ganglion cells. This cell death is mediated by oxidative stress. Their findings raise the possibility of use of antioxidants for delaying, preventing, or controlling some forms of glaucoma.
Retesting Visual Fields
Automated perimetry is often conducted on the same individual on a regular basis. Consequently, prior to testing, there is often existing visual field information for an individual patient. It is not clear if, or how, previous information is used in most commercial perimeters. Turpin et al. (p. 1627) detail a series of computer simulations designed to determine how results from previous tests can best be incorporated into perimetric procedures to improve accuracy and reduce variability. A new retest procedure is evaluated that significantly improves both accuracy and precision of testing and displays minimal bias, even when fields change and patients make errors.
Toll-like Receptors (TLR) in the Pathogenesis of Acute Anterior Uveitis
A selective perturbation in the expression and function of TLR2 and TLR4 has been demonstrated in patients with active acute anterior uveitis (AAU). The study of Chang et al. (p. 1711) implicates, for the first time, a role for TLRs in the pathogenesis of AAU. This provides new insights into the molecular mechanism by which microbial triggers may be involved in the development of uveitis and identifies a potential therapeutic target in clinical disease.
Long-Lasting Retinal Ischemic Tolerance
Preconditioning with brief hypoxia or ischemia can provide transient retinal neuroprotection from subsequent injurious ischemia. Zhu et al. (p. 1735) report their findings that in mice the duration of this neuroprotective, "ischemia-tolerant" phenotype can be extended to many weeks if preceded by multiple hypoxic preconditioning treatments. Long-lasting elevations in the retinal expression of the cytoprotectant heme oxygenase-1, secondary to extended increases in the transcription factor HIF-1a, are documented following this preconditioning regimen, which may contribute to this protracted phenotypic change. This unique form of plasticity may provide insights into reducing retinal neurodegeneration in the more chronic ischemic retinopathies.
Selective RPE Targeting with a Laser Scanner
Selectively targeting retinal pigment epithelium (RPE) cells, while preserving photoreceptors, is beneficial for treating retinal diseases that involve RPE dysfunction. By scanning a cw-laser beam rapidly across the rabbit retina and adjusting the scanning parameters, Framme et al. (p. 1782) demonstrate that the extent of cell injury can be controlled from individual RPE cell damage to mild photoreceptor coagulation. This flexibility is the key feature of the laser scanner that does not exist with current therapeutic methods. Future studies will demonstrate whether patients can benefit from a treatment that potentially can be tailored to individual needs.
Race, Lutein Supplements, and Macular Pigment Density in the Elderly
Iannaccone et al. (p. 1458) measured macular pigment optical density (MPOD) in a large (n = 222) biracial population of normal elderly (mean: 79 years old) individuals. Utilizing a heterochromatic flicker photometry (HFP)-based, simplified testing protocol, the authors obtained an MPOD estimate from 80% of the participants and found that users of lutein-containing supplements have an MPOD 21% higher than non-users, and blacks have 41% lower MPOD than whites. HFP-based MPOD measurements in epidemiologic investigations of the elderly, when the risk for macular degeneration is highest, are both feasible and informative.
Syngeneic Cell Transplants Preserve Vision
A major obstacle in the effort to use cell transplantation to treat retinal degenerative disease (RDD), is the host immune system. McGill et al. (p. 1906) have demonstrated that transplanting syngeneically-derived Schwann cells in a rat model of RDD can, without the use of immune suppressants, significantly preserve vision. This indicates that autologous transplantation of Schwann cells, without the need for suppression of the host immune system, could have significant therapeutic value in the treatment of human RDD.
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