| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| January 2005 | Inside IOVS | Volume 46/1 |
Deletion of a Guanylate Cyclase Gene Hinders Arrestin Translocation in Cones
Coleman and Semple-Rowland (p. 12) report that, in the guanylate cyclase-1 knockout mouse, cone arrestin fails to shift from the outer segment to the inner cell regions in the dark-adapted state, while rod translocation remains unaffected. These results show that translocation of phototransduction proteins in rod and cone cells is regulated by independent pathways.
Uveal and Cutaneous Melanoma: Connecting Two Worlds
Van Dinten et al. (p. 24) describe the categorization of uveal and cutaneous melanoma into a melanoma-associated antigen (MAA)-expressing panel and a MAA-deficient panel, on the basis of the expression characteristics of five MAAs. Their principal conclusion is that no differences in MAA expression were observed between uveal and cutaneous melanoma, thereby opening a perspective for a general immunotherapeutical approach for both types of melanoma. Additionally, many metastases show expression of MAAs, indicating that metastatic potential is not unequivocally correlated to silencing of these antigens.
Driving with Bioptic Telescopes
People with moderate visual acuity loss are permitted to use bioptic telescopes for driving in the USA. It has been suggested that the telescope is used only to pass the visual acuity test for licensure; however, the majority of bioptic drivers in the survey of Bowers et al. (p. 66) reported that the telescope met their driving needs, enabling them to perform driving tasks requiring resolution of fine detail and permitting relatively unrestricted driving patterns (85% of those 65 years old or younger drove to work). These findings provide evidence, from a social and economic perspective, in favor of allowing bioptic driving in countries (e.g., the European Union) where it is not currently permitted.
LPS Recognition by Corneal Fibroblasts
Corneal fibroblasts, the main cellular components of the corneal stroma, release chemokines and express adhesion molecules in response to stimulation by various cytokines. Invasion of bacteria or injection of lipopolysaccharide (LPS) into the corneal stroma also induces an acute inflammatory response. Kumagai et al. (p. 114) now show that human corneal fibroblasts express the LPS receptor complex and that LPS induces expression of intercellular adhesion molecule–1 and release of the chemokines interleukin-8 and monocyte chemotactic protein in these cells. These results suggest that corneal fibroblasts initiate the local infiltration of neutrophils and macrophages on detection of bacterial invasion.
Conjunctival Epithelial Stem Cells
Precise location and distribution of epithelial stem cells in the conjunctiva have not been determined, although fornix is reported to contain more stem cells than other areas. Nagasaki and Zhao (p. 126) present evidence that epithelial stem cells are distributed uniformly in the bulbar conjunctiva, based on the movement and the mitosis of epithelial cells as well as on the distribution of label-retaining cells. Additionally, their data suggest that the uniform stem cell distribution may be true in the entire conjunctiva. These findings may offer insight into the etiology and treatment of conjunctival anomalies such as pterygium.
Psychophysical Evaluation of Zebrafish Vision
The zebrafish has become a well studied model vertebrate in genetic studies of vision. Rinner et al. (p. 137) have developed a behavioral paradigm that allows the quantitative study of visual performance in zebrafish larvae. The study employs moving patterns projected onto a screen viewed by the immobilized larvae while recording evoked eye movements. With such a behavioral paradigm, aspects of visual performance such as visual acuity, contrast sensitivity, and light adaptation can be reliably quantified. This method will be useful to investigate mutant strains with subtle functional deficits by psychophysical means.
The Hyaluronic Acid Transmembrane Receptor and Glaucomatous Damage
Primary open-angle glaucoma (POAG) is a common neuro-degenerative disease characterized by selective retinal ganglion cell death. Choi et al. (p. 214) isolated a fragment of the hyaluronic acid transmembrane receptor CD44, i.e., soluble CD44 (sCD44), which is increased in the aqueous humor of patients with POAG. sCD44 was tested in cell culture and was cytotoxic to retinal ganglion and trabecular meshwork cells. The effects of sCD44 were blocked by either heat-denaturing or co-administration of anti-CD44 neutralizing antibody or hyaluronic acid. The results indicate that sCD44 is cytotoxic and a potential causative factor in the POAG disease process.
IP3 Receptors and Rod Bipolar Cell Function
Calcium signaling in retinal neurons is determined by intra- and extracellular sources for cytosolic free calcium. Koulen et al. (p. 292) show that the differential distribution of IP3 receptors in mammalian rod bipolar cells critically contributes to the signal properties of calcium transients in these retinal neurons and contributes to calcium-dependent functions of sub-cellular compartments. The findings of the study provide a potential mechanism for the adaptation of the ON-pathway of vision and for coincidence and threshold detection in retinal neurons.
Spontaneous Na+ Spikes in Human Photoreceptors
The sense of vision in humans is quite robust, and visual flickering is rarely experienced. To investigate this mechanism, Kawai et al. (p. 390) used the patch-clamp technique on isolated human cone and rod photoreceptors. Under current-clamp conditions, blocking h currents hyperpolarized the resting potentials of cones and rods by ~10-15 mV and surprisingly generated spontaneous action potentials. The spontaneous spikes were blocked by tetrodotoxin, but not by Co2+, suggesting that they were Na+ spikes rather than Ca2+ spikes. The authors suggest that the h current may contribute to preventing visual flickering by inhibiting the generation of spontaneous Na+ spikes in human cones and rods.
Mutations in the TGFBI Gene and Granular and Lattice Corneal Dystrophies
Mutations in the TGFBI gene, encoding the protein keratoepithelin, result in granular and lattice corneal dystrophies. Chakravarthi et al. (p. 121) screened a series of Indian patients with granular and lattice dystrophy for mutations in this gene. They found three novel mutations in patients diagnosed with lattice corneal dystrophy, all located in the conserved fourth fasciclin-like domain of keratoepithelin. Clinical features associated with two of these mutations were atypical for lattice dystrophy. Data also suggest that, similar to other populations studied, the most common mutations underlying lattice and granular dystrophies are Arg124Cys and Arg555Trp, respectively. This study confirms the phenotypic specificity of the mutational hotspots in keratoepithelin and extends the range of mutational and phenotypic heterogeneity in this group of diseases.
Tetrathiomolybdate Inhibits Retinal Neovascularization
Elner et al. (p. 299) demonstrated that tetrathiomolybdate (TM), a copper-chelating agent, can inhibit retinal angiogenesis and vascular endothelial growth factor (VEGF) production in a mouse model of retinal neovascularization. Significant inhibition of retinal neovascularization and VEGF production was noted only if treatment with TM was started prior the development of retinal neovascularization. Treatment with TM did not affect the development of retinal neovascularization. TM inhibition of angiogenesis and VEGF may be mediated through inhibition of NF-kB activation, which is also important for the expression of other angiogenic agents, including IL-6, chemokines, MMP, and cell adhesion molecules.
Grating Acuity at Different Luminances in Wildtype Mice and in Mice Lacking Rod or Cone Function
The mouse became an important model in vision research even though it is not predominantly a visual animal. A major question is not only what the visual acuity of a mouse might be but also whether spatial vision is used preferentially at higher or lower light levels. Using a newly developed automated optomotor paradigm, Schmucker et al. (p. 398) studied grating acuity in wildtype mice and in mutant mice lacking rods, cones, or both. They found that mice rely on spatial vision only at higher luminances (even though the optics of the eye produces a very bright retinal image). Furthermore, spatial vision was dominated by rod, rather than cone, input, since mutants lacking cones performed similarly as the wildtype, whereas mutants lacking rods had poor spatial vision. Finally, the melanopsin pigment system in the mouse retina does not mediate spatial vision since double mutants without rods and cones did not respond to the optomotor drum.
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |