In-Brief  |   December 2000
Lighting the Way to Better Ocular Therapies
Investigative Ophthalmology & Visual Science December 2000, Vol.41, f4-F5. doi:
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      Lighting the Way to Better Ocular Therapies. Invest. Ophthalmol. Vis. Sci. 2000;41(13):f4-F5.

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      © ARVO (1962-2015); The Authors (2016-present)

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Azithromycin and Trachoma
Antibiotics are an important part of WHO strategies for the global elimination of trachoma (still the world’s commonest form of preventable blindness) by the year 2020. The finding by Bowman et al. (p. 4074) that a single oral dose of azithromycin (costing £3.20 per child) is more effective than 6 weeks of tetracycline ointment (costing£ 0.21) for children with trachoma under operational conditions has important implications. The difference is particularly marked for intense inflammatory disease, thought to be a predictor of future blinding complications. Azithromycin is unaffordable by countries in which trachoma is prevalent and is currently donated by Pfizer and the International Trachoma Initiative to five countries. These results should encourage the extension of the donation program. 
Gene Therapy and Glaucoma
Glaucoma filtration surgery can fail due to excessive scarring in conjunctival or scleral tissues. Angella et al. (p. 4158) report that plasmid-mediated transfection of filtration tissues is enhanced 30-fold over injection of plasmid in saline by absorbing plasmid DNA into a collagen shield placed into the filtration bleb. Reporter gene activity is highly restricted to bleb tissues with minimal activity in the cornea, iris-ciliary body, and conjunctiva located opposite the bleb site. Short-term gene therapy using plasmid DNA and a simple collagen shield delivery vehicle may be useful for delivering therapeutic oligonucleotide sequences for regulating wound healing following glaucoma surgery. 
Complement Regulators and Inflammation
Three membrane-bound complement regulatory proteins, namely membrane cofactor protein (MCP), decay acceleration factor (DAF), and membrane attack complex inhibiting protein (CD59), are differentially expressed in the human eye. Sohn et al. (p. 4195) report that normal human aqueous humor and vitreous contain soluble forms of MCP, DAF, and CD59, which are functionally active. Thus, identification of membrane-bound and soluble complement regulatory proteins in normal human eye provides evidence that a regulatory system exists to protect these cells from destruction by complement activating events during an inflammatory response. Additionally, soluble complement regulators may be therapeutically useful in suppression of intraocular inflammation and tissue damage. 
IL-1ra and Graft Rejection
IL-1ra is a natural cytokine that is highly effective in promoting corneal allograft survival. Yamada et al. (p. 4203) demonstrate that, whereas IL-1ra promotes induction of tolerance to intracameral antigens, it does not lead to a tolerizing response to transplantation antigens, underscoring that suppression of allosensitization does not necessarily lead to long-term immunological tolerance. Since induction of tolerance to corneal alloantigens is believed to occur naturally, but after considerable time post transplantation, these data suggest that from a clinical standpoint, treatment with IL-1ra may be required for at least several months after surgery to prevent most cases of graft rejection. 
HGF and Cataract
If we are to provide a rational basis for preventing posterior capsule opacification (PCO), we first need to understand the mechanisms regulating lens cell growth following cataract surgery. Wormstone et al. (p. 4216) provide evidence that hepatocyte growth factor (HGF) signaling through its receptor c-met can induce proliferation, migration, and protein synthesis of human lens cells. Furthermore, detection of HGF and c-met in serum-free cultured human capsular bags suggests both a potential autocrine and paracrine role for HGF in PCO formation. The HGF/c-met signaling system therefore could provide a useful target for future strategies of prevention. 
Channel Blockers and PVR
During proliferative vitreoretinopathy (PVR), Müller glial cells become proliferative. Since the amount of intracellular calcium is crucial to the rate of proliferation, one may assume that a block of certain ion channels may influence Müller cell proliferation. Indeed, Kodal et al. (p. 4262) found that during epidermal growth factor stimulation, calcium ions enter the Müller cells likely via voltage-gated calcium channels, and the amount of calcium ions that pass the plasma membranes is regulated by the activity of calcium-activated potassium channels. The block of both channel types may be a therapeutic tool to prevent excessive Müller cell proliferation. 
Stem Cells and the Retina
Nishida et al. (p. 4268) transplanted hippocampus-derived neural stem cells into the vitreous cavities of rats’ eyes just after the retinas were mechanically injured. As early as 1 week after transplantation, the stem cells were found to migrate and incorporate into the hosts’ retinas around the injured sites. Immunohistochemically, some of them expressed neuronal and glial markers. Immunoelectron microscopy revealed the formation of synapse-like structures between graft and host cells. The data suggest that by the manipulation of mechanical injury, integration into thehosts’ retinas and differentiation of the grafted stem cells can be achieved, even in adult rat eyes. 
Oxygen and ROP (Revisited)
Current animal models of retinopathy of prematurity (ROP) use large, prolonged swings of extreme oxygen concentrations which are very effective at inducing retinal abnormalities. These oxygen swings, however, do not reflect the oxygen changes preterm infants experience clinically. Cunningham et al. (p. 4275) have used oxygen fluctuations in a rat which were exactly translated from a preterm neonate that developed severe ROP. The oxygen changes are small, frequent, vary around normal, and cause reduced central capillary density and reduced peripheral vascularity, early features of ROP that can lead to neovascularization. Oxygen fluctuation alone appears to be sufficient to disrupt normal retinal vascularization, and the authors believe that reducing oxygen fluctuation in neonates might lower the incidence and severity of clinical ROP. 
Air Infusion and Vitrectomy
A postoperative visual field defect is one of the serious complications possible after vitrectomy. Hasumura et al. (p. 4300) tested the hypothesis that the complication’s main cause is mechanical retinal damage from air infusion during and after fluid-air exchange. Sharply demarcated retinal lesions were observed at the opposite side from the infusion cannula in rabbit eyes where a fluid-air exchange was performed. The lesion showed detachment of internal limiting membrane and the exposed nerve fiber layer. The inner retina was most affected, with concomitant swelling of the inner plexiform layer and the inner granular layer. Increased infusion air pressure was accompanied by a significant increase in the area of retinal damage. The authors stress the importance of preventing direct mechanical stress to the retina caused by the infusion air during vitrectomy. Decreasing the air pressure is a crucial technique, as well as using humidified air, to decrease mechanical retinal damage. 

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