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| February 2006 | Inside IOVS | Volume 47/2 |
Genetic Factors in Age-Related Macular Degeneration
The common variant Y402H in the complement factor H gene is known to be a major determinant of risk for age-related macular degeneration. Smoking is also a well established risk factor. Sepp et al. (p. 536) show that the association with Y402H is similar for geographic atrophy and choroidal neovascularization and for smokers and non-smokers. Heavier smokers with the CC genotype may be particularly at risk. Unraveling the genetic factors predisposing to age-related macular degeneration is providing insights into the pathogenesis of this condition.
Tissue Engineered Epithelial Sheets and Excimer Laser Photoablation
Currently, a major complication to excimer laser photoablation is the associated post-operative corneal haze. Hayashida et al. (p. 552) evaluated the possibility of a new approach for laser keratectomy in combination with the transplantation of tissue-engineered epithelial cell sheets. The transplanted cell sheets form stable attachment to the laser-ablated stromal bed and provide an intact epithelial barrier immediately after surgery. Both one and two months postoperatively, corneal haze was also significantly inhibited compared to control groups receiving only laser photoablation. This method presents a promising approach for the reduction of postoperative haze that is a common occurrence after laser keratectomy.
A New Single Cell Microinjection Technique
An important technical goal in the age of nanotechnology is to develop the ability to inject a particular substance into a single living cell or a surface layer of cells without damage. Sonoda et al. (p. 558) describe success in injecting genes into cells by ultrasound-bursted microbubbles. Bursting microbubbles in the cornea with ultrasound acoustic pressure produced high-velocity micro-sized liquid jets that could hit surrounding tissues. This phenomenon allowed genes to penetrate the cell membrane, thus acting as if they had been injected by a micro- or nano-sized syringe. The transparent corneal tissue provided an excellent model to demonstrate the practicability of this technology. This result presents new possibilities for progress in a number of areas, based on the physiology of single cells in living tissues.
Glutamate Modulation of Glaucomatous RGC Apoptosis
Glutamate release has been implicated in retinal ganglion cell (RGC) death in glaucoma. Guo et al. (p. 626) have assessed different glutamate-modulation strategies using a technique of imaging RGC apoptosis in vivo. They demonstrate that a staurosporine-induced RGC apoptosis model is a useful screening tool for potential neuroprotective therapies, and they also show that a specific agent targeting Group II metabotropic (mGluR) receptors may be useful in preventing glaucoma-related RGC death. Finally using combination therapies, they suggest that approaches to minimize the effects of secondary RGC degeneration should be considered among therapies for glaucoma.
Nuclear Transport of GRb is Chaperoned by Hsp90
Glucocorticoid receptor b is involved in regulating glucocorticoid-b receptor nuclear transcriptional activity in trabecular meshwork (TM) cells, and its absence contributes to glucocorticoid hyper-responsiveness. Zhang et al. (p. 700) have shown that GRb transport from the cytosol to the nucleus utilizes heat shock protein (Hsp)90 as a chaperone as part of a constitutive pathway that moves GRb into the nucleus in the absence of glucocorticoid binding. In normal and glaucomatous TM cells, the nuclear concentration of Hsp90 is correlated with the nuclear expression of GRb. Overexpression of GRb results in an enhanced accumulation of Hsp90 in the nucleus. Whereas, inhibition of Hsp90 activity with 17-AAG blocks GRb transport and consequently leads to GRb degradation through the proteasome pathway. These data provide strong evidence that Hsp90 is required for the nuclear transport of GRb, and changes in the nuclear concentration of GRb could influence steroid responses, including enhancing glucocorticoid responsiveness in patients with glaucoma.
Anatomic Compartmentalization of Growth Factors in Retinal Development
Vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-I, and growth hormone (GH) are important regulators of physical growth, as well as normal and pathologic retinal development. The rat retina develops postnatally and is mature by postnatal day (P)21. Modanlou et al. (p. 738) performed ontogenic examination of serum, vitreous fluid and retinal VEGF, IGF-I and GH during normal rat retinal development from birth to P21. Their studies showed compartment-specific differences. VEGF and IGF were coordinately involved in rat retinal development, with vitreous fluid as a reservoir. The role of GH in rat retinal development was unclear. These findings suggest that compartmental differences should be considered in conditions such as retinopathy of prematurity.
Cellular Changes in Extraocular Muscles Following Strabismus Surgery
A common treatment for motility disorders of the extraocular muscles (EOM) is resection, a surgical shortening of the muscle. Christiansen and McLoon (p. 605) performed surgical resection on one superior rectus muscle, which allows examination of surgical shortening of one rectus muscle and passive stretch on its ipsilateral antagonist. In both muscles, there were increases in the number of myofibers positive for neonatal myosin heavy chain isoforms (MyHC) and in the numbers of brdU positive myonuclei and MyoD positive satellite cells. Thus, surgically produced active and passive stretch on the EOM upregulates satellite cell activation, integration of new myonuclei into existing myofibers, and upregulation of immature MyHC. Understanding the effects of strabismus surgery on myofiber biology and remodeling may suggest new approaches to improving surgical outcomes.
Rapid Technique for Grading Optic Nerve Damage
Rodent models of chronic optic neuropathy are providing important clues on the cellular and extracellular changes in the retina and optic nerve in glaucoma. They are also shedding light on new avenues for intervention. Evaluation of optic nerve damage in models of glaucoma often require time-consuming methods. Chauhan et al. (p. 634) describe a rapid (~1 min/nerve), effective and reproducible technique of optic nerve grading that could potentially avoid the substantial delays that can occur in the assessment of optic nerve damage and the initiation of therapeutic intervention.
Visual Stimuli Influence Retinal Reflectance in Humans
Retinal diseases can affect retinal function before any anatomical change becomes apparent on ophthalmoscopy or retinal photography. In this study, Abràmoff et al. (p. 715) found evidence that visual stimuli can change the localized retinal reflectance to near infrared light in humans, and that these changes can be measured with a modified retinal camera. As a first step towards a technique for functional imaging of the retina, improvements in this methodology may lead to early diagnosis of selected retinal diseases.
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