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| May 2007 | Inside IOVS | Volume 48/5 |
Factors Influencing Eye Examination Behavior in African-Americans
Previous research shows that many people are not getting dilated retinal examinations according to recommended guidelines. Ellish et al. (p. 1989) conducted focus groups with African-Americans to identify factors that influence eye examination behavior. Cost was cited as the most important barrier to getting dilated retinal examinations, even for those with insurance. There was a lack of knowledge about glaucoma risk factors among this high-risk population, and participants reported waiting until they were experiencing a vision problem before seeing an eye care professional. As the U.S. population ages, this lack of preventive eye care may lead to an increased incidence of eye disease.
ZO-1 Found in Nucleoli of Activated Corneal Fibroblasts
Although ZO-1 was named for its localization in tight junctions of epithelial cells, in corneal fibroblasts ZO-1's multiple PDZ protein-protein interaction domains provide links between actin and cell-cell junction proteins as well as between actin and integrins at the leading edge of lamellipodia. In a novel finding, Benezra et al. (p. 2043) report that ZO-1 localizes to nucleoli of serum-starved corneal fibroblasts treated with FBS, PDGF, or FGF-2 and in scrape-wounded corneal fibroblasts. These multiple sites of ZO-1 localization suggest two significant roles for ZO-1 in wound healing: nucleolar ZO-1 contributes to regulation of proliferation, and lamellipodial ZO-1 contributes to cell migration.
ROCK Inhibition and Wound Healing Activities of Tenon's Capsule Fibroblasts
The wound healing process is the major reason for failure after glaucoma filtration surgery. Tenon's capsule fibroblasts (TCFs) play a pivotal role in the occlusion of the created aqueous humor drainage channel. The Rho-kinase/ROCK signaling pathway is a key intracellular convergence point for signals initiating dynamic events involved in the wound healing process. Using H-1152P, a specific ROCK-inhibitor, Tura et al. (p. 2152) demonstrate the involvement of the ROCK-pathway in the proliferation, cytoskeletal organization, migration, and contractility of serum-stimulated human TCFs in vitro. These findings highlight the therapeutic potential of H-1152P as a safe and specific means to suppress the undesirable wound healing activities of TCFs.
Conjunctival M Cells as an Ocular Entry Point for Bacteria
The presence of antigen-sampling M cells in the mammalian conjunctiva has only been recently recognized. Petris et al. (p. 2172) now show receptor mediated transcytosis of bacteria by these cells. Translocation of microbes likely plays a role in the initiation of mucosal immune responses against commensal or transient ocular bacterial species. It also raises the likelihood that some opportunistic pathogens may use the conjunctival M cell as an entry point across the mucosal barrier just as they do in intestine and other mucosal locations.
Corneal Fibroblasts Inhibit Attack by Cytotoxic T Cells
Knickelbein et al. (p. 2194) demonstrate a novel immune regulatory mechanism by which corneal fibroblasts inhibit the proliferation and differentiation of cytotoxic CD8 T cells following infection with herpes simplex virus type 1, without diminishing their ability to secrete antiviral cytokines. Possibly as another mechanism of immune privilege, this strategy would allow continued secretion of antiviral cytokines to control the virus without destroying non-regenerating corneal stromal architecture. Further, several ocular immune pathologies, including herpes stromal keratitis and corneal graft rejection, appear to be mediated mainly by CD4, rather than CD8, T cells. These results also provide at least a partial explanation for this skewed response.
In Vivo Imaging of Human Retinal Pigment Epithelial Cells
Roorda et al. (p. 2297) employed high-resolution imaging with an adaptive optics scanning laser ophthalmoscope to obtain the first direct views of retinal pigment epithelial cells in living human eyes. The visibility of these cells indicates regions where the overlying photoreceptor array is compromised or missing, an observation that is further confirmed using fundus-based microperimetry. These findings will be of help in better understanding and establishing timelines in the development and progression of retinal degenerations.
Angiotensin Convertase, Bradykinin, and Choroidal Neovascularization
Angiotensin-converting enzyme (ACE), also known as kininase II, functions not only to convert angiotensin I to angiotensin II, but also to cleave bradykinin to inactive fragments. Nagai et al. (p. 2321) investigated the role of bradykinin in the development of laser-induced choroidal neovascularization (CNV) with or without ACE inhibition. ACE inhibition, but not bradykinin B2-receptor (B2-R) blockade alone, led to significant suppression of CNV. Interestingly, B2-R blockade together with high-dose of ACE inhibition resulted in more potent suppression of CNV than ACE inhibition alone. They showed a limited contribution of the kallikrein-kinin system to the development of CNV, in which the renin-angiotensin system plays more essential roles.
Inhibition of Retinal Neovascularization by Vitamin D
Vitamin D has inhibitory effects on a variety of cancers. It has been postulated that vitamin D may have antiangiogenic activity in some cancers. Albert et al. (p. 2327) show that vitamin D inhibited retinal neovascularization in vivo and retinal endothelial cell capillary morphogenesis in vitro. The antiangiogenic activity of vitamin D was dose-dependent. Side effects, which were not dose related, were increased serum calcium and lack of weight gain. Understanding the mechanisms of vitamin D action in retinal endothelial cells may aid in the development of new strategies for the treatment of ocular diseases with a neovascular component, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration.
Monosomy 3 and Network Vasculogenic Mimicry Patterns in Uveal Melanoma
Monosomy 3 and network vasculogenic mimicry patterns are strongly associated with death from metastases spread in uveal melanoma patients. Networks are usually confined to areas within the tumor while intratumor distribution of monosomy 3 is unknown. Meir et al. (p. 1918) applied laser capture microscopy followed by microsatellite analysis to characterize monosomy 3 in two distinct areas from 15 uveal melanomas. In each tumor containing networks there was monosomy 3 in both areas which were tested despite the existence of networks in only one area. This suggests that monosomy 3 is strongly associated with networks and that it may contribute but is not sufficient for their development.
Strabismologists Beware: Body Rotation Gives the Eye a Lasting Twist
Eye twisting around the line of sight is ordinarily limited by Listing's Law to a predictable amount. Using 3-D magnetic search coil recordings, Crane et al. (p. 2076) found that the amount of ocular twist can be changed by rotating the whole body around a vertical axis. The new eye twist persists long after rotation ends and affects all horizontal and vertical eye positions equally. This means that the eye twist embodied in Listing's Law has a long memory for rotation sensed by the semicircular canals of the inner ear. Previous patient movements might confound clinical interpretation of eye twist.
Posterior Ocular Segment Drug Delivery by Various Periocular Routes
Periocular injection is an excellent route for posterior segment drug delivery with lower systemic side effects than oral or intravenous drugs and fewer ocular complications as compared to the intravitreal route. Ghate et al. (p. 2230) evaluated the pharmacokinetics of periocular injections, posterior subtenon (PST), retrobulbar and subconjunctival injections using ocular fluorophotometry with sodium fluorescein(NaF). The authors found that the NaF diffused trans-sclerally from the depot into the posterior segment. The orbital vasculature played a greater role in NaF clearance than the choroid and the PST route had the highest vitreous drug levels with the lowest systemic levels.
Computer Diagnosis of Retinal Lesions: Lipid Exudates and Cotton Wool Spots
Computer diagnosis of retinal images is going to play an important role in the prevention of visual loss and blindness. So far, the emphasis is on detection and classification of diabetic retinopathy, and numerous algorithms for the detection of hemorrhages and microaneurysms in color fundus images have been published. Exudates and cotton-wool spots (superficial retinal infarcts) are much harder to detect, and are easily confused with drusen, the hallmark lesions of age-related macular degeneration, even by experienced clinicians. In a preliminary study, Niemeijer et al. (p. 2260) introduce an algorithm that can detect these "bright lesions" in retinal color images, and additionally differentiate these three types of lesions, with a performance comparable to experienced clinicians. In the future, similar algorithms may be used in research, to automatically grade fundus images of patients with diabetic retinopathy or age-related macular degeneration, or in clinic, for semi-automatic diagnosis and classification of diabetic retinopathy.
Alzheimer's Disease: Early Manifestations in the Retina
A means to detect the early signs of Alzheimer's Disease (AD) is of considerable clinical importance because treatments applied early will likely be the most effective. Because it is accessible to sensitive, noninvasive optical diagnostic methodologies, the retina is an excellent site for the detection of the very earliest structural and functional abnormalities in AD. Berisha et al. (p. 2285) show that retinal abnormalities in patients with early AD include a specific pattern of retinal nerve fiber layer thinning, narrow retinal veins, and decreased blood flow in these veins, all measureable quantities that can provide a set of objective biomarkers for early AD.
Functional Vision in Chinese Readers Might Be Inferred with Snellen E Acuity
Letter acuity charts are used in western countries for evaluation of functional vision. In China, such a language-specific chart is unavailable. The Chinese national standard optotype for acuity measurement is Snellen E, simpler than most Chinese characters (CCs). Zhang et al. (p. 2383) investigated the legibility of representative CCs, and the relationships between CC acuities and Snellen E acuities with simulated refractive errors. The acuity vs. defocus functions of simple, medium, and complex CCs and Snellen Es were found to parallel each other. This research suggests a potentially valid way to infer functional vision in Chinese readers with Snellen E acuity.
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