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Inside IOVS 2001
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June 2001 |
Moving from the Lab to the Clinic
TGF-b and Epithelial Repair
Cells migrating to cover a corneal epithelial wound exit the cell cycle and express elevated levels of the cell cycle inhibitor p15INK4b. Zieske et al. (p. 1465) examined if the spatial and temporal expression of TGF-b receptors were involved in these processes. Results showed that both TbR-I and TbR-II were upregulated after wounding. TbR-II increased in cells that migrated to cover the wound area, whereas, TbR-I was upregulated across the entire cornea. Furthermore, TGF-b1 stimulated p15INK4b expression. These data indicate that TbR-II-mediated signaling stimulates the expression of genes such as p15INK4b that results in spatial separation of migration and proliferation during epithelial repair.
PLCg1 and Epithelial Growth
Islam and Akhtar (p. 1472) demonstrate a positive correlation between upregulation of PLCg1 activity and proliferation of rabbit corneal epithelial cells (RCEC) treated with EGF. The EGF-stimulated PLCg1 activation involved both increased synthesis and tyrosine phosphorylation of the enzyme. Treatment of RCEC with PI3K inhibitors inhibited both EGF-stimulated PLCg1 activation and cell proliferation. The data suggest possible involvement of PLCg1 and PI3K in EGF-stimulated wound repair in corneal epithelium.
Unoprostone and Retinal Arteries
Using isolated, perfused segments of pig retinal arteries, Yu et al. (p. 1499) show that the docosanoid, unoprostone isopropyl (Rescula®), exerts a dilatory effect on endothelin-1 contracted vessels. These vasoactive properties of unoprostone isopropyl are superior to those of prostaglandins (PG) such as PGF2a and thromboxane in terms of any likely benefit to retinal blood flow, in addition to any reduction in IOP.
Hsps and Glaucoma
Heat shock proteins (Hsps) enhance cell survival and increase neuronal tolerance to ischemic damage. Park et al. (p. 1522) demonstrate that induction of Hsp72 in retinal ganglion cells in an experimental rat glaucoma model with heat stress or systemic zinc administration increases survival of RGCs. These results suggest the possibility of a novel therapeutic approach to glaucoma through an enhanced induction of the endogenous heat shock response.
Interferon-b and Scarring
Inflammation is an important risk factor for the failure of glaucoma filtration surgery. Chang et al. (p. 1531) demonstrate that human Tenon’s fibroblast (HTF) produce interferon-b which prevents T-cell apoptosis. Even mitomycin-C or 5-fluorouracil-treated HTFs were able to prevent this type of apoptosis. This study suggests that this particular fibroblast-T-cell interaction may play a role in mediating the development of chronic inflammation and persistent conjunctival scarring.
ATIII and Uveitis
Recently, antithrombin III (ATIII) has been shown to have antiangiogenic, antitumor and anti-inflammatory activities. In the present study, Yamashiro et al. (p. 1553) demonstrate that ATIII suppressed leukocyte rolling and subsequent leukocyte infiltration during endotoxin-induced uveitis. It is suggested that ATIII suppresses leukocyte rolling by inhibiting P-selectin expression resulting in attenuation of leukocyte infiltration. Thus, ATIII may be useful in the management of patients with uveitis.
Mydriasis Potentiation
This double-masked investigation by Ghose et al. (p. 1581) revealed that preinstillation of the topical anesthetic 4% lignocaine 3 minutes before a drop of 1% tropicamide significantly increased both the degree and rapidity of mydriasis without any reduction in media clarity. Investigating the possible pathomechanism showed changes in Schirmer values, break-up time and corneal thickness after lignocaine, indicating corneal microepithelial damage and reduced tearing. Both may enhance intraocular penetration and hence potentiation.
Photoreceptor Protection by PEDF
Cao et al. (p. 1646) demonstrate that the intravitreal injection of pigment epithelium-derived factor (PEDF) results in significant protection of photoreceptor cells from light-induced death. PEDF, when used in combination with basic fibroblast growth factor, enhances the functional status of photoreceptor cells beyond the protection provided by either factor alone.
Photoreceptor Protection by Steroids
The transcription factor AP-1 is essential for light-induced apoptosis as evidenced by studies in knockout animals. Wenzel et al. (p. 1653) show that inhibition of AP-1 activity in genetically normal mice by pharmacological activation of the glucocorticoid receptor completely protects retinal function and morphology. Thus, despite presence of a stimulus that normally leads to apoptosis, photoreceptors may effectively be protected against degeneration by interference with apoptotic signal transduction.
Photoreceptor Transplantation
Woch et al. (p. 1669) show that transplanting fetal rat retina into the subretinal space of a rat model of retinal photoreceptor degeneration results in visually evoked responses in a CNS structure that receives direct input from retinal ganglion cells. The mechanism responsible remains to be determined. Perhaps, this central visual response results from increased synaptic efficacy within the host retina that could be a result of functional connections with the transplant. [Abstract] [Full Text]
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