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| April 2005 | Inside IOVS | Volume 46/4 |
Unique Lipid Environment of Detergent-Resistant Membranes from Rod Outer Segments
Growing evidence suggests that photoreceptor membranes contain discrete, laterally segregated domains called lipid rafts. Detergent-resistant membranes, biochemical isolates of presumptive lipid rafts, can be isolated from rod outer segment membranes and have been shown to contain a number of proteins important for photoreceptor structure and function. Martin et al. (p. 1147) provide a detailed characterization of the lipid composition of detergent-resistant membranes isolated from rod outer segments. The lipid environment of these membrane domains may regulate the localization and function of raft-associated proteins.
A Novel Tissue Adhesive for the Synthesis of Corneal Wounds
Chondroitin sulfate, a glycosaminoglycan present in many human tissues, has been found to have interesting tissue adhesive properties after activation with an aldehyde. Based on these findings, Reyes et al. (p. 1247) performed initial studies of the application of chondroitin sulfate for the purpose of uniting the edges of corneal incisions. The adhesive strength was found to be superior to that of 10-0 nylon sutures in the authors' ex vivo trials. Wound healing studies in other tissues (cartilage) have shown no additional wound contraction using this adhesive, which may be particularly appealing for corneal synthesis. Currently the authors are testing toxicity and wound healing issues in live models of corneal incisions.
Optic Nerve Head Blood Flow Decreases with Increasing Age
In the process of aging, various organ systems are affected in the human body. Histological studies of the optic nerve head described alterations suggesting a vascular impairment with increasing age. In the study by Boehm et al. (p. 1291) it was shown by the use of laser Doppler flowmetry that optic nerve head blood flow is reduced 4-8% per decade suggesting a reduction of optic nerve head blood supply in the elderly. Whether this physiological reduction of optic nerve head blood flow due to age contributes to a higher risk of the elderly of developing glaucomatous optic nerve damage needs to be verified in further studies.
Pseudomonas, Rafts, and Contact Lens-Associated Infection
Yamamoto et al. (p. 1348) demonstrate that normal corneal surface epithelial cells do not exhibit lipid raft structures; but contact lens wear and not exposure to Pseudomonas alone induces raft formation, aggregation, and internalization of bacteria in vivo and in vitro. Blocking raft formation is a new potential strategy for preventing contact lens-associated infection in the corneal epithelium, and is separate and distinct from strategies preventing Pseudomonas' binding to a variety of surface protein receptors such as cystic fibrosis transmembrane conductance regulator and Toll-like receptors.
Why and How Does the Human Lens Pigment?
Sigma receptors have no known homology with other membrane receptors, but appear to be located in the endoplasmic reticulum (ER). They are upregulated in tumors and fast growing cells. Wang et al. (p. 1403) show that the Sigma-1 receptor is expressed in the human lens and that Sigma-1 receptor antagonists such as BD 1047 can inhibit lens cell growth. Surprisingly, lens cells appeared to accumulate pigment granules in the presence of the antagonist. Pigment granules provide a protective role in many cell types and although the lens is normally devoid of pigment, granules 'of unknown origin' have been reported in certain aged lenses and cataracts. This study further reports that the antagonists induce the formation of pigment granules by stimulating an existing and probably normally protective melanin synthesis pathway in the human lens involving tyrosine incorporation, tyrosinase, and tyrosinase-related proteins 1 and 2. Sigma receptors through their location in the ER may control not only the output of this pathway, but also the growth of cells.
Autoregulation of Blood Flow in the Optic Nerve Head
Autoregulation of blood flow against the changes in perfusion pressure in the optic nerve head (ONH) should play a vital role in the pathogenesis of glaucoma. Its mechanisms and temporal properties, however, have not been fully understood. Takayama et al. (p. 1409) demonstrate, using a high time-resolution analysis of ONH circulation with the laser speckle method, that autoregulation in the rabbit ONH is achieved within several seconds after an acute decrease in IOP, and the response is significantly impaired by systemic administration of a calcium channel blocker, but not by a nitric oxide synthase inhibitor, indomethacin, or sympathetic nerve amputation.
CFTR Facilitates Ocular Surface Chloride Secretion
Direct evidence for ocular surface chloride secretion through the Cystic Fibrosis Transmembrane Regulator (CFTR) is presented by Levin and Verkman (p. 1428). The authors developed methodology for measuring open-circuit potential differences (PDs) across corneal and conjunctival epithelia of living mice. CFTR activators and inhibitors and ionic substitutions were used for measurements in wild-type mice and transgenic mice lacking functional CFTR. CFTR was found to be a major chloride transporting pathway. The authors suggest that CFTR-specific activators warrant evaluation as potential therapeutics for keratoconjunctivitis sicca.
Calcium-Dependent Cell Contacts and Growth Factor Expression in RPE Cells
In aging, the effects of accumulated oxidative stress cause RPE cells to undergo apoptosis. As reported in the present study by Wang et al. (p. 1508), the loss of calcium-dependent cell-cell contacts significantly increases the gene expression of VEGF, bFGF, and other angiogenic factors and decreases the gene expression of PEDF in RPE cells in vitro. These results provide a mechanism by which surviving RPE cells in the aged eye may promote choroidal neovascularization (CNV) by a chronic shift in the balance of growth factors towards angiogenesis.
CCR5 Mediates Recruitment of Langerhans Cells
Chemokine and chemokine receptor are critical factors that mediate the effect of proinflammatory cytokines on the recruitment of MHC class II+ Langerhans cells. Yamagami et al. (p. 1201) investigated chemokine and chemokine receptor expression and function involving Langerhans cells migration in the mouse corneal epithelium after cautery. They found that CCR5 and its ligands play a critical role in mediating recruitment and mobilization of MHC class II+ Langerhans cells in the mouse corneal epithelium. Targeting CCR5 and its ligands may serve as a potential new strategy to modulate immunity of ocular surface.
The Vasorelaxing Effect of CGRP and Natriuretic Peptides in Isolated Bovine Retinal Arteries
Boussery et al. (p. 1420) explored the characteristics of the vasodilation induced by calcitonin gene-related peptide (CGRP) and by natriuretic peptides in isolated bovine retinal arteries (BRAs). Their results confirm that CGRP potently relaxes BRAs and demonstrate that endothelium-derived NO, voltage-dependent K+ channels, and possibly also CGRP1-receptors are involved. Furthermore, this study contradicts the hypothesis that natriuretic peptides could regulate retinal blood flow through a direct vasorelaxing effect on retinal arteries, since none of the natriuretic peptides dilates BRAs.
Rat Strain Differences in Neovascular Retinopathy
Neovascularization is common to many human retinal disorders – from retinopathy of prematurity (ROP) to exudative macular degeneration and diabetic retinopathy. Disease-specific risk factors often fail to fully account for individual variation in the susceptibility to neovascularization. The study by van Wijngaarden et al. (p. 1445) identifies strain-dependent differences in the susceptibility of inbred rats to oxygen-induced retinopathy, a model of ROP. They speculate that characterization of the genetic determinants of this variation may prove useful for stratifying risk in the human proliferative retinopathies.
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