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Inside IOVS 2001
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May 2001 |
Cell Biology: Importance in Vision Research
Cellular Signatures of Melanoma
Morphologic features of uveal melanomas, especially nucleolar size, are important for predicting the outcome of patients with uveal melanoma. Moshari and McLean’s (p. 1160) method of measurement of the longest nucleoli using the silver stain for nucleolar organizing regions (AgNOR) in microscopic sections of uveal melanoma provides a cheap and highly significant prognostic indicator. Silver staining facilitates the detection of irregularly shaped nucleoli, which are probably associated with tumors that metastasize and kill. This information can be used in the future, along with other prognostic variables such as tumor size and cell type, to help predict patient survival.
NP-1 and Flk-1 in ROP
Neuropilin-1 (NP-1), a semaphorin receptor for chemorepulsive axon guidance, has been reported to play an important role for the VEGF signaling by binding to VEGF165 and enhances its binding to Flk-1. Ishihama et al. (p. 1172) demonstrated that NP-1 and Flk-1 are co-expressed in retinal neovascularization in a mouse model of retinopathy of prematurity (ROP). The restricted expression of Flk-1 and NP-1 on neovascularized vessels suggests that these molecules may play important roles in retinal neovascularization. This is the first report of the co-localization of NP-1 and Flk-1 on neovascularized vessels of the retina from ROP mice.
Stromal Biology in the Cornea
A healthy cornea's transparency is due in part to the remarkable organization of keratan sulfate and chondroitin sulfate proteoglycans produced by stromal keratocytes. Berryhill et al. (p. 1201) have found that adult bovine keratocytes cultured under serum-free conditions secrete the known corneal proteoglycans decorin, lumican, keratocan and osteoglycin-mimecan. Additionally, the authors demonstrate that prostaglandin D synthase, a known retinoid-binding protein, is secreted as a keratan sulfate proteoglycan in vitro and manufactured as a glycoprotein in native corneal tissue. This characterization of the in vitro keratocyte system shows that these cells are capable of maintaining an in situ phenotype in culture. Such a system will be useful in further understanding stromal biology and the mechanisms by which transparency is maintained.
Corneal Architecture and Microbial Spread
The pattern of bacterial spread within the human cornea is not normally visible being masked by the host inflammatory response. By inoculating human corneal buttons, maintained in organ culture with different bacteria, Butler et al. (p. 1243) demonstrated that bacterial spread within the cornea is determined by the compact architecture of the stromal collagen. If the corneal stroma is allowed to swell before inoculation, globular colonies of bacteria were observed. In non-turgid, compact corneal buttons, a linear arborizing pattern forming a branching network of bacterial colonies was observed. This model has considerable potential in further understanding host-microbe interactions and microbial spread that occurs during infection.
GST Antibodies and Glaucoma
Recent studies suggest that autoantibodies are present and increased in the sera of patients with glaucoma and some of these may have pathogenic significance. Here, two-dimensional gel Western blot analysis against bovine retinal fractions using sera from patients with glaucoma identified a 29-kD band present in the soluble fraction as Glutathione S-transferase (GST) by electro-spray mass spectrometry. Anti-GST antibodies were found in the serum of 34 of 65 glaucoma patients (52%) and 5 of 25 controls (20%). Using ELISA, Yang et al. (p. 1273) found that glaucoma patients had higher titers of anti-GST antibody compared to control patients. These findings indicate that GST is yet an additional retinal antigen targeted by the serum antibodies detected in numerous patients with glaucoma.
NO and HSV
Infection of the cornea with herpes simplex virus (HSV) results in a recurrent immune-mediated inflammatory response known as herpetic stromal keratitis (HSK). Productive infection with HSV is crucial for HSK manifestation. Nitric oxide (NO) is a free radical gaseous molecule that is a mediator of vital physiological functions. Benencia et al. (p. 1277) observed that inhibiting NO production during HSV ocular infection of Balb/c induced an increase in both morbility and mortality. Thus, NO production in response to viral infection may be one of the mechanisms of innate immunity involved in limiting viral replication after ocular infection with HSV.
FGF AND PCO
Posterior capsule opacification (PCO) is a progressive growth condition that leads to a secondary loss of vision following surgery in cataract patients. Recent work published in IOVS indicated that a major reason for the very robust growth underlying PCO arose from putative autocrine control factors. In the present issue, Wormstone et al. (p. 1305) identified a major contribution from basic fibroblast growth factor (bFGF) since disruption of signaling using a specific inhibitor can retard growth. It, therefore, appears that FGF is an important protein in lens autocrine regulation and provides a target for strategies to prevent PCO.
A2E and RPE Atrophy
The death of retinal pigmented epithelial (RPE) cells in a number of retinal disorders, including Stargardt's disease, Best's disease, some forms of retinitis pigmentosa and atrophic age-related macular degeneration (AMD), is significant in terms of disease progression. Sparrow and Cai (p. 1356) report that the cell death program that is initiated in A2E-containing cells in response to blue light involves the activation of caspase-3 and can be suppressed by upregulated expression of Bcl-2. Future efforts to protect RPE cells from atrophy depends on continued efforts to understand the molecular pathways involved in executing RPE cell death.
PBN and Retinal Degeneration
Although encouraging results have been found in animal models of retinal degeneration, there is currently no treatment for humans. A safe and effective drug that could be administered systemically would have potential application. Ranchon et al. (p. 1375) show that intraperitoneal injections of phenyl-N-tert-butylnitrone (PBN), a well-defined free radical trapper, protects the morphological and functional properties of the rat retina against the damaging effects of light exposure. Since oxidative processes may also play a role in inherited retinal degenerations and age-related macular degeneration, PBN or related compounds could be candidates for treating these blinding diseases.
LASIK and Image Blur
LASIK surgery has become a popular alternative for compensation of conventional refractive errors. Now, attention is brought to high order aberrations, optical imperfections uncorrectable by standard means. Unlike corneal topography or visual performance, ocular aberrations are not typically measured in the clinic to evaluate surgical outcomes. Moreno-Barriuso et al. (p. 1396) show an increase (by a factor of ~2) in third order and higher aberrations, particularly spherical aberration (by a factor of ~4), following standard myopic LASIK surgery. These aberrations cause image blur, particularly for dilated pupils. Improved surgical algorithms, attempting to achieve perfect correction, should first avoid the generation of spherical aberration, as current surgeries do.
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