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| July 2005 | Inside IOVS | Volume 46/7 |
Chromosomal Deletions and Prognosis in Uveal Melanoma
Uveal melanoma is a highly malignant disease with a mortality of 50% at 10-15 years. The study of Kilic et al. (p. 2253), which is the largest cohort of patients studied to date for cytogenetic abnormalities in primary uveal melanoma, demonstrates that concurrent loss of chromosome arms 1p and 3 is an independent predictor of decreased disease-free survival. Their findings suggest that chromosomal abnormalities may be useful in identifying patients at high risk of metastases. Nevertheless, for the identification of patients at high risk, prospective trials using samples retrieved by fine needle aspiration biopsy may be valuable.
Anti-inflammatory Effects of the Herbal Extract Triptolide
Triptolide, consisting of extracts of the herb Tripterygium wilfordii hook f, has been used in traditional Chinese medicine for the treatment of rheumatoid arthritis. Lu et al. (p. 2346) show that, like dexamethasone, triptolide inhibits IL-8 and MCP-1 expression in cultured human corneal fibroblasts exposed to proinflammatory cytokines, an action likely mediated by inhibition of NF-kB activation. Similar effects of triptolide in vivo might be expected to limit the infiltration of neutrophils and monocytes into the cornea.
Role of the Basement Membrane in Corneal Wound Healing
While it has been assumed that all corneal wounds heal with similar mechanisms, Hutcheon et al. (p. 2362) show that the presence or absence of a basement membrane has a dramatic effect on transforming growth factor (TGF)-b signaling. To demonstrate this difference, TGF-b signaling proteins SMAD 2 and 4 were localized in two wound models. While little if any SMAD activation was seen in a debridement model, extensive nuclear translocation of both SMAD 2 and 4 was observed in a superficial keratectomy model. This localization correlated with the absence of the basement membrane marker laminin. These data suggest that wound type affects the healing response.
Statins Increase Aqueous Humor Outflow
Song et al. (p. 2424) report that perfusion of organ-cultured anterior segments of porcine eyes with cholesterol-lowering statins increases aqueous humor outflow by lowering isoprenoid lipid intermediates essential for Rho GTPase function. Previous studies have demonstrated that inhibition of the Rho/Rho kinase pathway in the trabecular meshwork increases aqueous humor outflow facility. This study provides a biochemical and mechanistic link between the effects of statins and Rho GTPase activity in causing these effects, and suggests that statins might be therapeutically effective in lowering IOP in glaucoma patients.
Why Does Acanthamoeba Keratitis Not Progress to the Interior of the Eye?
Acanthamoeba keratitis is a protozoal infection that produces extensive damage to the ocular surface, sometimes requiring transplantation to restore vision. While Acanthamoeba nasopharyngeal and cutaneous infections can progress to encephalitis, Acanthamoeba ocular infections remain restricted to the cornea. Clarke et al. (p. 2472) show that a robust neutrophil response is associated with the disappearance of intraocular trophozoites and suggests that cells of the innate immune apparatus are important in preventing Acanthamoeba keratitis from becoming an intraocular infection. A better understanding of the pathogenic cascade of Acanthamoeba keratitis may lead to new techniques to prevent and treat parasitic corneal infections.
Unexpected Role of Fas Ligand in Intraocular Staphylococcus aureus Infection
Engelbert and Gilmore (p. 2479) used a murine model of endophthalmitis to show that, contrary to expectations, complement plays a minor role in host defense against intraocular S. aureus infection. Unexpectedly, Fas ligand, a molecule that has been implicated mainly in suppressing adaptive immunity, exhibited an important immunostimulatory role, providing resistance to infection. The role of Fas ligand in protection against infection was not previously known. These findings begin to provide a rationale for the design of therapies to modulate the host response to infection in a disease that is invariably sight threatening.
Increased IOP Differentially Affects Simple and Complex Cortical Cells
Chen et al. (p. 2611) studied responses of neurons in the cat's visual cortex to grating before and during brief elevation of the intraocular pressure (IOP). The responses of all cortical cells declined during elevation of IOP. However, the decreased responses of simple cells were always substantially greater than those of complex cells. The differential decrease between the two cell types was independent of a cell's receptive field location and cortical depth. The differential effects are general and may originate from the retina through the lateral geniculate nucleus, where different effects of elevation of IOP are found on X and Y type retinal ganglion cells.
Humphrey Matrix Frequency-Doubling (FDT2) Perimetry in Glaucoma
Artes et al. (p. 2451) investigated threshold and variability characteristics of the Humphrey Matrix, the second generation frequency-doubling technology (FDT) perimeter, in glaucoma patients. Their study shows that the close relationship between the threshold estimates of FDT2 and standard perimetry at normal visual field locations breaks down within damaged parts of the visual field. In contrast to standard automated perimetry, FDT2 has constant test-retest variability across its entire measurement range, and, in spite of its smaller range of stimulus contrasts, does not suffer from larger floor effects. These properties might provide clinical advantages for monitoring patients with glaucoma.
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