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| November 2005 | Inside IOVS | Volume 46/11 |
T Cells Drive Orbital Fibroblast Proliferation in Graves' Ophthalmopathy
Graves' ophthalmopathy (GO) is an autoimmune process in which fibroblasts in orbital tissue proliferate excessively, resulting in forward protrusion of the eye, accompanied by pain, double vision, and nerve and muscle damage. Feldon et al. (p. 3913) report that proliferation of orbital fibroblasts from Graves' patients is driven by the patients' own T cells, in part mediated by CD40-CD40 ligand interactions. Therefore, inhibiting interactions between T cells and fibroblasts represents a target for novel nonsurgical therapies for GO. Blocking costimulation via the CD40-CD40 ligand pathway, which shows promise to prevent transplant rejection, may have substantial benefits in GO as well.
Glucagon Inhibits Eye Growth in the Chick
Glucagon amacrine cells in the chick retina may play an important role in visual regulation of postnatal eye growth. Previous studies implicate the release of retinal glucagon and activation of a glucagon receptor in mediating an ocular "stop"-growth signal. The results of this study by Vessey et al. (p. 3922) are consistent with the hypothesis that endogenous glucagon inhibits excessive eye growth and myopia, and promotes thickening of the choroid, in the chick. These findings have implications for understanding the retinal mechanisms underlying ocular growth and myopia development.
Carbogen Breathing and Acetazolamide May Benefit Ischemic Disorders of the Optic Nerve
Placing oxygen-sensitive microelectrodes at <50 µm from the optic disc of mini-pigs over intervascular areas, Petropoulos et al. (p. 4139) found that carbogen breathing increases optic disc PO2 significantly, more than hyperoxia, whereas the maximal increase is obtained by concomitant use of carbogen breathing and intravenously injected acetazolamide by producing a higher systemic PaCO2. In cases of disturbed perfusion through capillaries, this association can improve optic nerve head (ONH) oxygenation by increasing O2 diffusion from the ONH arterioles. Hence, it could be beneficial for disorders related to ONH ischemia or blood flow dysregulation, like ischemic optic neuropathy and glaucoma. Clinical studies are needed to confirm the above promising results.
The Prostanoid FP-Receptor and Intraocular Pressure (IOP) Control
Ota et al. (p. 4159) investigated the contribution of FP-receptors on IOP using prostanoid FP-receptor-deficient mouse eyes with presumed functional uveoscleral outflow pathways. The baseline IOP of FP-receptor-deficient mice was similar to that of wild type control mice. A single application of latanoprost, travoprost, bimatoprost, or unoprostone had no effect on lowering the IOP in FP-receptor-deficient mice. The prostanoid FP-receptor plays a crucial role in the mechanism of early IOP-lowering by all commercially available prostaglandin analogues.
Roots & Wings: Mesenchymal Cell Origins in a Mammalian Eye
Identification of the embryonic origins of mature cell lineages, as well as determining lineage-specific expression of key regulatory genes, are key steps towards understanding eye development. Gage et. al. (p. 4200) use transgenic approaches in mice to provide the first long-term fate maps of neural crest and mesoderm in a model mammalian eye. The eventual fates of the two embryonic precursor pools are similar, but not identical, to those in birds. Five key transcription factor genes have unique expression patterns between neural crest and mesoderm. These results provide important new models for understanding eye development and disease.
Cytokine Profiles in Uveitis
Uveitis is a group of diseases characterized by sight-threatening intraocular inflammation. Many studies have identified elevations of inflammatory cytokines and chemokines in uveitis aqueous humor but were severely restricted by the small sample volumes available. Curnow et al. (p. 4251) used multiplex bead immunoassays to measure simultaneously over 15 different cytokines and chemokines. The results show a distinct molecular pattern in idiopathic uveitis and define those molecules most likely to be involved in disease pathogenesis. This emerging technology provides a powerful approach to the study of complex molecular patterns and has potential applications across a wide range of diseases.
Visual Acuity Change and Mortality
Freeman et al. (p. 4040) found an increased risk of mortality in people with visual acuity impairment. If the relationship between acuity and mortality is indeed causal, it likely acts via numerous pathways through a variety of intervening variables. Future work using large datasets should investigate how vision loss is associated with different causes of mortality, examine whether factors such as a clinical diagnosis of depression, falls, or other accidents act as intervening variables in this relationship, and examine why this relationship may be limited to women. The identification of these factors could give additional targets for intervention if acuity cannot be restored.
Effect of Retinoic Acid on Human Conjunctival Epithelial Cells
Retinoic acid is essential to maintaining the wet-surfaced phenotype of the ocular surface epithelia, possibly through a complex mechanism involving the regulation of many genes. Hori et al. (p. 4050) have used microarray technology to identify specific genes regulated by retinoic acid in cultured conjunctival epithelial cells. Their results indicate that the membrane-associated mucin MUC16 is highly responsive to retinoic acid treatment through group IIA secretory phospholipase - both genes being the most highly upregulated in the late phase of treatment. These findings indicate that regulation of the expression of hydrophilic mucins is an important factor by which retinoic acid preserves a hydrated ocular surface epithelia.
Toll-Like Receptor-9 Modulates Pseudomonas aeruginosa Keratitis
Huang et al. (p. 4209) report the use of RNA interference (RNAi) technology to specifically silence Toll-like receptor-9 (TLR9) gene expression in corneas infected with P. aeruginosa. The data provide novel insight into the biological processes involved in the development of P. aeruginosa keratitis and show that silencing TLR9 signaling reduces inflammation, but may contribute to decreased bacterial clearance in the cornea.
Hepatocyte Growth Factor (HGF) Protects RPE from Apoptosis
In vitro studies show that oxidant-treated retinal pigment epithelium (RPE) cells undergo apoptosis, a possible mechanism by which RPE are lost in age-related macular degeneration. Therefore, the prevention of RPE apoptosis is of considerable therapeutic importance. Jin et al. (p. 4311) have imposed oxidative stress by GSH deficiency on RPE cells. The study shows that HGF partially blocks the induction of apoptosis by up-regulating antioxidant gene expression, improving cellular redox status, and inhibiting caspase-3-dependent cell death. Their findings suggest that HGF should be further evaluated for its therapeutic potential as an inhibitor of RPE apoptosis.
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