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| June 2005 | Inside IOVS | Volume 46/6 |
LPA and S1P Increase Corneal Barrier Function
The permeability of the corneal epithelium and endothelium is a critical determinant of corneal hydration and thus transparency. Yin and Watsky (p. 1927) use a technique not previously utilized in the cornea, electric cell-substrate impedance sensing (ECIS), to show that two members of the phospholipid growth factor family (PLGF), LPA and S1P, can increase the electrical resistance across cultured monolayers of these cells. As PLGFs have been found in both lacrimal fluid and aqueous humor, these lipids may play an important role in regulating the barrier function of the anterior and posterior cornea.
POAG Linked to Locus on Chromosome 15
A potentially major locus on chromosome 15 has been identified for primary open-angle glaucoma. Allingham et al. (p. 2002) found this locus by limiting their analysis to a clinically similar subset of patients—those exhibiting an early-adult age of onset. The mean age of those affected within this subset was approximately 44 years versus 61 for the remainder of the family dataset. There were no other phenotypic differences between groups. The early-adult onset POAG subset accounts for 17% of the total family dataset, making this potentially one of the largest genetic contributors to POAG reported to date.
Relationship of Cataract Grading Scores and Visual Impairment
Stifter et al. (p. 2071) found a strong association between the visual impairment of cataract patients and the severity of posterior subcapsular cataract and nuclear opacity. They were able to define precisely visual deficits from cataract grading scores. These findings pave the way for improving the clinical evaluation of cataract patients by pointing out the relevant impact of the type and morphology of lens opacities on vision. Besides the implications for the clinical evaluation of cataract patients before surgery and examinations for medical expertise, these new conclusions raise interest in the significance of cataract grading for planning ophthalmological studies, for both experimental and clinical research.
fC31 Integrase for Long-Term Non-Viral Gene Therapy
Non-viral approaches to gene therapy may be simpler and safer than viral methods; however, transgene expression has typically been transient. Chalberg et al. (p. 2140) used fC31 integrase to confer genomic integration and stable transgene expression following non-viral delivery by electroporation to rat RPE in vivo. The demonstration of long-term transgene expression suggests that fC31 integrase may be a simple and effective tool for gene therapy of the eye. The implications of this work are wide-ranging for retinal diseases, because this approach may provide a safe method that reduces the need for repeated administration of the therapeutic.
Ephrin/Eph Signaling in Pathological Neovascularization
Pathologic neovascularization is a component of many ocular diseases including retinopathy of prematurity, diabetic retinopathy, and AMD. Ephrin/Eph signaling molecules play a key role in vessel development and vascular patterning. In this study, Zamora et al. (p. 2175) demonstrate that intravitreal delivery of soluble EphrinB2 or EphB4 significantly reduces pathological neovascularization in a mouse model of oxygen-induced retinopathy. In addition, they found that intraretinal vessel development remains unaffected following this treatment. These studies provide evidence that these signaling molecules are involved in ocular pathological angiogenesis and may serve as novel therapeutic targets.
Incidence and Risk Factors of ARM in a Japanese Population
Miyazaki et al. (p. 1907) estimated the 5-year incidence and risk factors for age-related maculopathy (ARM) in a representative older Japanese population using the population-based cohort data. This study shows that the overall 5-year incidence of early ARM was 8.5%, and that of late ARM was 0.8%, and a higher age and smoking are relevant risk factors for early and late ARM in Japan. Because ARM is the most common cause of severe visual impairment among the elderly Japanese population, reducing the risk of this disease is another important reason to avoid smoking.
Macular Segmentation with OCT
As reported in Ishikawa et al. (p. 2012), segmentation of the StratusOCT macular scan with a new automated segmentation algorithm can objectively quantify glaucomatous damage to retinal ganglion cell and nerve fiber layers, and can discriminate between glaucomatous and normal eyes at least as well as conventional circumpapillary RNFL thickness measurement. The creation of a color thickness map of the macular region provides an easy-to-comprehend image, which facilitates interpretation of the location and magnitude of the glaucomatous damage.
A New Mouse Model of Diabetic Retinopathy
Modeling diabetic retinopathy in mice has been hampered by strain differences and an apparent insensitivity to streptozotocin. The Ins2Akita mouse is a spontaneously diabetic mutant that develops robust hyperglycemia 4-5 weeks after birth. While this mouse offers a convenient and predictable model of hypoinsulinemia, its potential as a model of diabetic complications has not been investigated. Barber et al. (p. 2210) report that the retinas of Ins2Akita mice develop several consequences of diabetes, including vascular permeability, acellular capillaries, microglial activation, apoptosis, reduced insulin receptor kinase activity and neurodegeneration, confirming this mouse as a new model of early retinal complications in diabetes.
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