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| February 2007 | Inside IOVS | Volume 48/2 |
Somatic Mosaicism for Arf Deletion Causes Primary Vitreous Hyperplasia
An earlier paper established that mice lacking the Arf tumor suppressor gene have "clinical" and pathological findings reminiscent of persistent hyperplastic primary vitreous (PHPV). In the current paper by Thornton et al. (p. 491), this same team shows that loss of Arf in only a subset of cells is a sufficient genetic insult to cause the same ocular pathology. Their findings indicate that Arf may have both cell autonomous and, possibly, non-cell autonomous effects during development. Further, the work provides evidence that somatic loss of a gene like Arf during human eye development might also result in PHPV.
Lens Cell Adhesion and Refraction
Lens intrinsic membrane protein-2 (Lim2) is structurally related to certain cell adhesion molecules known as claudins. Shiels et al. (p. 500) examined the lenses of mice lacking Lim2 and found that their internal refractive properties were significantly disturbed, resulting in image distortion. In addition, Lim2-negative lenses were more fragile than wild-type lenses and could be readily disaggregated into their component fiber cells, consistent with a loss of intercellular adhesion. These observations suggest that Lim2 provides a critical link between the cellular architecture and optical quality of the crystalline lens.
Ocular Carotenoid Levels in the Lutein Supplementation Era
Lutein supplements are commonly used by elderly patients at risk for visual loss from age-related macular degeneration, but clinical studies to date have shown variable and inconsistent macular responses to supplementation. Bhosale et al. (p. 543) measured carotenoid levels by HPLC in 228 eyes from 147 Utah donors and found that 18% of donors > 48 years of age had unusually high levels of lutein in the macula, peripheral retina, and lens. The vast majority of these outliers regularly consumed high-dose lutein supplements prior to death, a rare situation in the rest of the population. This study directly demonstrates that lutein supplementation can raise ocular carotenoid levels.
Risk Factors Associated with Progression to Constant Large-Angle Esotropia
Esotropia in infancy may initially present as a small-angle, variable-angle, or intermittent deviation. Infants who present with a constant small-angle or variable-angle esotropia seldom resolve and progress to a constant large-angle esotropia. However, infants with intermittent esodeviation have a high likelihood of spontaneous resolution. Fu et al. (p. 661) identified occlusion therapy and abnormal stereoacuity as risk factors for the progression from intermittent esotropia to constant large-angle esotropia. These factors are possibly interrelated. The result suggests that part-time occlusion therapy may be sufficient to degrade stereoacuity or produce stereoblindness.
Potential Importance of BMP-7 Signaling Modulation in Glaucoma Therapy
The increase in outflow resistance in primary open-angle glaucoma (POAG) is associated with changes in the amount and quality of the extracellular matrix (ECM) in the trabecular meshwork (TM), which are under the influence of TGF-b2 signaling. Fuchshofer et al. (p. 715) provide evidence that the effects of TGF-b2 on ECM turnover in TM cells are strongly inhibited by BMP-7. Based on their data it is reasonable to assume that BMP-7 modulates and antagonizes the effects of TGF-b2 signaling on TM outflow resistance. The pharmacological modulation of BMP-7 signaling in the TM might be a promising strategy to treat POAG.
Simvastatin Dilates Porcine Retinal Arterioles by an NO-Mediated Pathway
Recent studies suggest that HMG-CoA reductase inhibitors (statins) may have beneficial effects on vascular protection beyond cholesterol reduction. The authors recently demonstrated that simvastatin increases retinal blood flow in humans. In this study, Nagaoka et al. (p. 825) they examined the direct effect and the underlying mechanism for the vasomotor action of simvastatin in retinal arterioles. Simvastatin elicits mainly an endothelium-dependent, NO-mediated dilation of porcine retinal arterioles. It appears that inhibition of the mevalonate-Rho kinase pathway in endothelial cells contributes in part to the simvastatin-induced vasodilation.
Unstable Fellow Eye Adaptation, Not Fatigue, Confounds Perimetric Results
Perimetry is an essential test for patients with eye diseases such as glaucoma. It is commonly believed that short perimetric tests decrease the influence of subject fatigue, thereby resulting in more reliable results. However, Anderson and McKendrick (p. 943) show that previous reports of reduced visual field sensitivity over time may not in fact be the result of fatigue, but rather of unstable adaptation in the fellow, patched eye. This result has important implications when developing new test procedures, where concentrating on controlling adaptation, rather than shortening test length, may improve test reliability.
MicroRNAs Present in the Mammalian Eye
One major outcome of the human genome project was the evidence that there are small fragments of the genome that, although they do not produce proteins, exert an important role in regulating the function of many genes and proteins. These fragments, termed "microRNAs," have recently been shown to be essential for the formation of many organs of the body. To date, however, nothing is known about their function in the eye. In this article Karali et al. (p. 509) show that some microRNAs are expressed in the eye, suggesting that they may contribute to its formation and function, both in physiological and pathological conditions.
Proteomic and Transcriptomic Analyses of Retinal Pigment Epithelial Cells Exposed to TFPI-2
TFPI-2 has been previously reported as growth-promoting factor for RPE cells. Shibuya et al. (p. 516) performed proteomic and transcriptomic analysis on TFPI-2-treated and non-treated human primary RPE cells. Proteomic analysis revealed c-myc binding proteins and ribosomal proteins L11 preferentially induced by TFPI-2. Among the up-regulated transcripts were c-myc, Mdm2, transcription factor E2F3, retinoblastoma binding protein, and p21 gene, which are associated with the c-myc binding protein and ribosomal protein L11. TFPI-2 may promote proliferation of RPE cells by augmented c-myc synthesis and the activation of E2F in the Rb/E2F pathway at the G1 phase.
A Neural Basis for Cross-Axis Eye Movements in Monkeys with A-Pattern Exotropia
Das and Mustari (p. 665) have recorded from oculomotor neurons related to vertical eye movements in juvenile monkeys with A-pattern exotropia and dissociated vertical deviation (DVD). These animals had previously been rendered strabismic by disrupting binocular vision during the critical period for visual development. Vertical motoneuron activity within the oculomotor nucleus was strongly correlated with the inappropriate vertical eye movements in the non-fixating eye observed during a horizontal tracking task. The results suggest that, in animals with sensory-induced strabismus, altered innervation to extraocular muscles from motor nuclei produces the inappropriate cross-axis eye movements, resulting in change in ocular misalignment with gaze position.
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