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| September 2006 | Inside IOVS | Volume 47/9 |
Novel IMPDH1 Retinal Proteins
Bowne et al. (p. 3754) report identification and characterization of novel IMPDH1 proteins in human and mouse retinas. IMPDH1 poses a dilemma because mutations in this highly conserved, widely expressed enzyme only cause retinal diseases, such as autosomal dominant retinitis pigmentosa and Leber congenital amaurosis. These findings may provide an explanation. The authors propose that the mutations affect the novel retinal proteins, not the canonical IMPDH1 protein which has been studied for many years. They also report differences in the abundance of human and mouse IMPDH1 isoforms, suggesting that mouse may not be a good model for human IMPDH1 diseases.
SAGE of Rat Limbal and Corneal Epithelia
The basal epithelial cells of the corneal limbus are enriched in corneal stem cells. Adachi et al. (p. 3801) compared the transcripts present in the rat limbal and central corneal epithelia by serial analysis of gene expression (SAGE). Of nearly 4000 annotated transcripts, approximately one-fifth were limbal specific, one-fifth corneal specific, and three-fifths overlapping in the two epithelial regions. Limbal-enriched transcripts (WDNM1-like protein, mesothelin, marapsin) suggest that the limbal epithelial cells are associated with cellular proliferation and migration. These cellular properties are consistent with previous reports that corneal cancers are confined to the limbal region.
Transplantation of a Cultivated Human Conjunctival Epithelium
Tanioka et al. (p. 3820) evaluated the suitability of transplanted cultivated human conjunctival epithelium (HCjE) as a corneal epithelial replacement in rabbits with total corneal and limbal deficiency. Both the cultivated HCjE and the engrafted epithelium manifested 5-6 layers of stratified squamous epithelium similar in morphology to normal corneal epithelium. This report clearly demonstrates the potential of cultivated HCjE as an alternative tissue source for corneal epithelial replacement. This animal study is a step toward the eventual transplantation of autologous cultivated HCjE to treat patients with ocular surface disorders.
Unusual Neuromuscular Junctions in Extraocular Muscles
A combination of laser capture microscopy and RT-PCR reveals unusual properties of extraocular muscle neuromuscular junctions, including segregation of the fetal gamma and adult epsilon acetylcholine receptor subunits into multiply and singly innervated fibers, respectively; the presence of neuronal acetylcholine receptor subunits in extraocular muscles; and the presence of the myogenic regulatory factor, myogenin, in multiply innervated fibers. As reported in Fraterman et al. (p. 3828), these unusual properties may underlie the susceptibility or resistance of extraocular muscles to certain myasthenic syndromes and may also contribute to the unique characteristics of neuromuscular transmission seen in these muscles.
PEDF Modulates Macrophage Activation
Pigment epithelial-derived factor (PEDF) is a known potent antiangiogenic factor, which has recently been shown to reduce proinflammatory cytokines in the eye. The anti-inflammatory mechanisms of action of PEDF are not known. Since macrophages mediate inflammation and are both antiangiogenic and proangiogenic, determining the influence of PEDF on behavior of these innate immune cells becomes an important issue. Zamiri et al. (p. 3912) demonstrated that PEDF enhances IL-10 and inhibits IL-12 and nitric oxide production by LPS-activated macrophages. PEDF also significantly reduced ear swelling in the mouse model of endotoxin-induced inflammation. By modulating macrophage activation, PEDF may an essential factor to straddle inflammation and angiogenesis.
An Angiogenesis Inhibitor Induced by VEGF
ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs) has been demonstrated to inhibit angiogenesis in vivo and to suppress endothelial cell proliferation in vitro. Xu et al. (p. 4059) have shown that ADAMTS1 mRNA and protein are increased in a mouse model of ischemia-induced retinal neovascularization. Furthermore, VEGF induced both time- and dose-dependent increase in ADAMTS1 mRNA and protein in endothelial cells in a PKC-dependent fashion. Knockdown of endogenous ADAMTS1 resulted in increased proliferation of endothelial cells. These results indicate that VEGF-upregulation of ADAMTS1, a potent angiogenesis inhibitor, may represent a mechanism for feedback inhibition of angiogenesis and retinal neovascularization.
Electron Avalanche Transfection: A Novel Method for Nonviral Gene Transfection
Chalberg et al. (p. 4083) demonstrate a new technique for nonviral gene delivery called electron avalanche transfection. This method combines an electric field with tensile stress to permeabilize cells. The authors demonstrate successful use of the technique in a model system as well as in rabbit retina in vivo, and show that it is more efficient and produces less cellular damage than electroporation. Because it appears safe and provides advantages over current methods, electron avalanche transfection has the potential to succeed across many applications both in vivo and ex vivo, including the introduction of DNA, siRNA, protein, and small molecules to a wide variety of cell types.
Complement Factor H Expression in Ocular Tissues
Complement factor H (CFH) is a component of the mammalian complement system, which regulates the alternative pathway of complement activation and protects the host cell from inappropriate complement activation. A variation in human CFH, Y402H, has been shown to be associated with an increased risk of developing age-related macular degeneration. Mandal and Ayyagari (p. 4091) observed in human and mouse eye that CFH is expressed in the distalmost 3 mm of the optic nerve and in the RPE, ciliary body, photoreceptors, and retinal arteries. A gradual increase in the expression of CFH with age is observed in the mouse eye. RPE produces the highest level of CFH in the eye and the higher local concentration of CFH in the RPE might have a role in protecting the retina and RPE from indiscriminate complement activation due to inflammatory insults.
Unique Multifocal ERG Findings of CRB1 Carriers of Leber Congenital Amaurosis
Leber congenital amaurosis (LCA) is a multigene group of disorders with clinical variability. Seven LCA genes have been described with more genes expected. As gene-specific clinical trials are approaching, early and rapid genotyping of LCA patients will be essential. Yzer et al. (p. 3736) developed a new system by phenotyping the obligate heterozygous carrier parents to suggest the causal LCA gene in affected offsprings. They demonstrate that CRB1 carriers have a phenotype on multifocal ERG testing, which reveals a regional retinal dysfunction, unlike other LCA carriers. The regional nature of the dysfunction was predicted by the CRB1 animal models.
Discontinuing Tamsulosin Does Not Prevent Floppy Iris in Cataract Surgery
The a1-adrenoreceptor antagonist tamsulosin, a medication prescribed for the treatment of lower urinary tract symptoms of benign prostatic hyperplasia or, in women, urinary
retention, has been found to cause annoying floppy iris-related complications, i.e., intraoperative floppy iris syndrome (IFIS), during cataract surgery. Pärssinen et al. (p. 3766) report that all of their cataract patients who had been using tamsulosin from 6 months to 10 years had IFIS. The severity of IFIS was not related to the concentration of tamsulosin in serum or in the aqueous humour. Interruption of medication for 7 to 28 days caused patients urinary difficulties and did not eliminate IFIS.
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