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David G Charteris

Publications and source records attributed to David G Charteris.

22 records · Page 2Linked to original sources

Experimental retinal reattachment: a new perspective.

In the feline model, retinal detachment initiates a cascade of changes that include photoreceptor- cell "deconstruction," apoptotic death of some photoreceptors, neurite outgrowth from second- and third-order neurons, remodeling of photoreceptor synaptic terminals, and Müller-cell gliosis. We have previously shown that reattachment within 24 h halts or reverses many of these presumed detrimental changes. However, in patients with retinal detachments, reattachment cannot always be performed within this 24-h window. Moreover, recovery of vision following successful reattachment surgery in the macula is often imperfect. Here, we examine the ability of relatively long-term reattachment (28 d) to stop or reverse several cellular events that occur at 3 d of detachment. In contrast to earlier studies of reattachment, which focused on the regeneration of outer segments, we focus our attention here on other cellular events such as neuronal remodeling and gliosis. Some of these changes are reversed by reattachment, but reattachment itself appears to stimulate other changes that are not associated with detachment. The implications of these events for the return of vision are unknown, but they do indicate that simply reattaching the retina does not return the retina to its pre-detachment state within 28 d.

Animals↗

Differential expression of matrix metalloproteinases 2 and 9 by glial Müller cells: response to soluble and extracellular matrix-bound tumor necrosis factor-alpha.

Glial Müller cells are known to undergo functional and morphological changes during retinal proliferative disorders, but very little is known of the contribution of these cells to extracellular matrix deposition during retinal wound healing and gliosis. This study constitutes the first demonstration that retinal Müller cells express two major matrix metalloproteinases (MMPs), gelatinase A (MMP-2) and gelatinase B (MMP-9), implicated in cell migration and matrix degradation. Although mRNA and gelatinolytic activity of MMP-2 remained unchanged in cultured Müller cells, basal levels of MMP-9 mRNA observed after subculture at 24 hours, markedly declined after 48 or 72 hours. This correlated with the expression of MMP-9 gelatinolytic activity that peaked at 24 hours, but gradually decreased at 48 and 72 hours. Tumor necrosis factor-alpha, in both a soluble form or bound to collagen and fibronectin, increased MMP-9 mRNA and gelatinolytic activity, but not MMP-2 expression, and its effect could be blocked by anti-tumor necrosis factor-alpha antibodies. The results suggest that Müller cells may aid in the local control of extracellular matrix deposition during retinal proliferative disorders, and that interaction of these cells with matrix-bound cytokine may influence their pathological behavior. Control of Müller cell production of MMP-9 may constitute an important target for the design of new therapeutic approaches to treat and prevent retinal proliferative disease.

Adult↗

The ability of rapid retinal reattachment to stop or reverse the cellular and molecular events initiated by detachment.

PURPOSE: To determine the effects of reattachment on the molecular and cellular events initiated by a retinal detachment lasting 1 hour or 1 day. METHODS: Experimental retinal detachments were created in the right eyes of nine cats. Reattachments were performed 1 hour (n = 3) or 1 day (n = 3) after the detachment, and the animals were killed 3 days after detachment. Three-day detached (n = 3) and normal (n = 3) retinas were used for comparisons. Agarose-embedded sections were double labeled with a panel of antibodies. Some sections were also probed with the TUNEL technique to detect apoptotic cells. Wax-embedded sections were labeled with the MIB-1 antibody to the Ki67 protein to detect proliferating cells. RESULTS: The 1-hour and 1-day detachments followed by reattachment showed a very similar and consistent reduction in photoreceptor deconstruction and the Müller cell gliotic response when compared with 3-day retinal detachments without reattachment. Light microscopy and immunolabeling with opsin antibodies showed a significant reduction in both rod and cone outer segment (OS) degeneration, even though OS length was shorter than normal. The reattachments also showed a reduction in opsin redistribution, retraction of rod terminals, TUNEL-labeled photoreceptors, loss of cytochrome oxidase staining in photoreceptors, neurite outgrowth from second-order neurons, the number of proliferating cells, and the increase in intermediate filaments and loss of soluble proteins from Müller cells. The apparent re-ensheathing of the OS by the apical processes of the retinal pigment epithelium had begun but was not completely normal. CONCLUSIONS: These data indicate that, even though the length of the OS is less than normal, retinal reattachment within 1 day of detachment can either greatly retard or reverse many of the molecular and cellular changes initiated by detachment.

Animals↗

Proliferative vitreoretinopathy: developments in pathogenesis and treatment.

Proliferative vitreoretinopathy is an abnormal wound-healing response following retinal detachment and occurs in 5% to 10% of cases. It is now possible to treat this once-blinding condition. However, proliferative vitreoretinopathy still remains the most common cause of failure to reattach the retina. Recent work has helped to unravel the causes of proliferative vitreoretinopathy, and new adjuvant treatments are being evaluated to improve the success rate of retinal reattachment surgery, both anatomically and functionally. At present, preventative treatment has only been found to work in high-risk cases. It is hoped that improvement in targeted immunosupression will eventually reduce the incidence of proliferative vitreoretinopathy. At the current time, the management of proliferative vitreoretinopathy still remains a surgical skill.

Humans↗