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| February 2003 | Inside IOVS | Volume 44/2 |
Eyes Compensate for Spectacle Lenses Despite Massive Astigmatic Blur
If chicks or monkeys are made myopic or far-sighted by positive or negative spectacle lenses, their eye growth changes so that they compensate for the optical effect of the lenses, a process thought to be similar to the spontaneous correction of neonatal hyperopia or myopia that occurs in human infants. Does the eye need to know the sign of the defocus to accomplish this compensation or is the image quality an adequate cue? McLean and Wallman (p. 449) show that even if the image is degraded by powerful astigmatic lenses or by mild diffusers, the compensation for positive or negative spectacle lenses is essentially normal. This argues that the eye can discern the sign of the blur and that this information is more important than the amount of blur.
In Vivo Time-Lapse Microscopy for Studying Movement of Corneal Epithelial Cells
Corneal epithelium of adult GFP mice exhibits a pattern of GFP expression that is suitable for tracking cell movement. As reported in Nagasaki and Zhao (p. 558), epithelial GFP could be imaged and followed by in vivo time-lapse microscopy in a living mouse, which demonstrated constant centripetal movement of epithelial cells at the basal or supra-basal layers at an average rate of 26 mm/day. The same technique can be used to investigate movement of epithelial stem cells and their progeny from the limbus into the cornea, and also movement of corneal epithelial cells after an injury in a living animal.
Inhibition of Corneal Neovascularization in CCR5 "Knockout" Mice
Corneal neovascularization in a clinically relevant model of corneal injury was inhibited in mice with a targeted disruption (gene "knockout") of CCR5, a chemokine receptor involved in leukocyte and endothelial chemotaxis. Ambati et al. (p. 590) showed that the inhibition was sustained and correlated with reduction of VEGF expression. This finding could advance the management of blinding disorders such as Stevens-Johnson syndrome, cicatricial pemphigoid, corneal allograft rejection, and corneal injury from infection, trauma, or alkali.
Age-Related Differences in the Pathophysiology of Amblyopia
Davis et al. (p. 610) report that the electrophysiological and psychophysical changes associated with strabismic amblyopia of onset before or after 18 months of age are very different. This indicates that the pathophysiological changes produced in the central visual pathways by a squint are very different at these different ages and are likely to depend on the underlying stage of visual development. If age of onset is not taken into account in studies of amblyopia, then important abnormalities may be missed. It may be that the optimum treatment strategy for amblyopia is different with different ages of onset.
HCMV Hides in Retinal Pigment Epithelial (RPE) Cells To Be Ignored by Cytotoxic T L Lymphocytes
Host defense against infection by human cytomegalovirus (HCMV) is ensured in great part by cytotoxic CD8+ T lymphocytes (CTL) directed against the tegument protein pp65. The hyperimmediate release of incoming pp65 into MHC class I pathway following fusion of the virus with the cell membrane provides a very early mechanism of defense. In RPE cells, HCMV is known to enter through endocytosis, providing the virus with a hiding-place to elude immune surveillance. Allart et al. (p. 665) showed that, even though RPE cells have the ability to process an endogenously delivered pp65 into peptides and to present epitopes to CTL, they were not lysed by cytotoxic T lymphocytes. Impaired killing of infected RPE cells could contribute to favor constitution of HCMV reservoirs within the retina.
Metals and Protective Genes in Aging Human Lenses
Toxic metals are implicated in degenerative diseases including cataract. Hawse et al. (p. 672) demonstrate that specific metallothionein and alpha-crystallin/sHSP protective genes are differentially induced in human lens epithelial cells by specific metals implicated in degenerative diseases. In contrast to cataractous lenses that accumulate toxic metals, clear human lenses did not accumulate toxic metals with age, with the exception of iron that decreased over 80% with age. The results implicate metallothioneins and alpha-crystallin/sHSPs in protection and/or regulation of toxic metals and they provide the groundwork for further understanding the roles of these genes in cataract.
Effect of Acute Hyperglycemia on Retinal Oxygenation
It has been uncertain whether the retina exhibits the Crabtree effect, the inhibition of respiration by glycolysis at elevated glucose levels. Padnick-Silver and Linsenmeier (p. 745), showed that photoreceptor oxygen consumption, recorded with microelectrodes in the cat retina in vivo, was no different during acute hyperglycemia than during normoglycemia. Choriocapillaris PO2 decreased during hyperglycemia (by ~6 mm Hg), which led to an increase in the fraction of photoreceptor O2 derived from the retinal circulation. Average inner retinal PO2 did not change, suggesting that the inner retinal hypoxia found early in diabetes is probably not a direct consequence of hyperglycemia.
A Transactivator that Produces Cell-Specific Modulation of Retinal Gene Expression
Angeletti et al. (p. 755) generated transgenic mice expressing a transactivator (tTA1) specifically in photoreceptor cells with an onset time similar to endogenous Rhodopsin. These mice allow to easily switch off transcription of the gene of interest in the retina in a short time frame simply by feeding the mice with doxycycline. Histological and electrophysiological studies demonstrate that tTA1 is not toxic in the retina. This genetic system will allow driving transcription in a cell specific and time controllable manner. These mice are suitable for the study of factors involved in retinal biology and of mutant forms of genes involved in retinal pathology.
Visual or Computer-Assisted Detection of Diabetic Retinopathy: Which is Better?
A new computerized method of identifying diabetic retinopathy on digitized fundus photographs is shown by Larsen et al. (p. 767) to be able to closely match the sensitivity and specificity of routine visual grading. The routine grader appears to emphasize specificity over sensitivity, but when allowed to see candidate lesions marked by the computer, the grader’s sensitivity increases considerably, from 76.4% to 91.0%. The method may be used to alert the attention of retinopathy graders to fundus lesions that are otherwise overlooked in high-volume routine grading.
Mer Gene Dysfunction Inhibits Photoreceptor Phagocytosis by RPE in Mice
The retinal pigment epithelium (RPE) of RCS rats fails to phagocytize photoreceptor outer segments because of a mutation in the Mertk gene. Duncan et al. (p. 826) have found that ablation of Mer function in mice results in a retinal degeneration phenotype almost identical to that of RCS rats. The similarity in phenotypes suggests that an RPE phagocytic defect underlies all retinal degeneration caused by loss of function of the Mer tyrosine kinase, perhaps including human patients with mutations in MERTK. This mouse model may be particularly useful for studying the role of Mer in photoreceptor-RPE cell interactions, phagocytosis and retinal degeneration, given the powerful tools available for genetic studies in mice.
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