Search

The effect of treatment with a broad-spectrum inhibitor (BB1101) of the matrix metalloproteinases (MMPs) on nerve regeneration and functional recovery after nerve crush was examined. Drug treatment had no effect on latency but from 63 days the compound muscle action potential was significantly increased and was no different to that in the sham-operated controls at 72 days. Levels of MMP mRNA expression, and the localisation and activity of MMP proteins, were examined in rats for a 2 month period following a nerve crush injury, and compared with sham-operated controls. The mRNA of all the MMPs studied was up-regulated by 5-10 days after nerve crush, and they remained up-regulated for 40-63 days, except for MMP-9 which was down-regulated by 10 days. MMP immunoreactivity was localised to Schwann cells, macrophages and endothelial cells, and with the exception of membrane type 1-MMP (MT1-MMP), it was more intense after nerve crush compared with sham-operated controls. Regenerating axons showed immunoreactivity for MMP-2 and MMP-3. In situ zymography confirmed that the activity of MMPs in the nerve was increased following crush but that the activity was greatly reduced in rats treated with BB-1101. Thus despite the inhibition of MMPs by BB-1101, the drug did not appear to essentially affect nerve degeneration or regeneration following nerve crush but that it could be beneficial in promoting the more effective reinnervation of muscles possibly by actions at the level of the muscles.

The matrix metalloproteinases (MMPs) are a large family of zinc-dependent enzymes which are able to degrade the protein components of the extracellular matrix. They can be placed into subgroups based on structural similarities and substrate specificity. Aberrant expression of these destructive enzymes has been implicated in the pathogenesis of immune-mediated neuroinflammatory disorders. In this study we investigate the involvement of MMPs, from each subgroup, in Wallerian degeneration in both the central and peripheral nervous systems. Wallerian degeneration describes the process initiated by transection of a nerve fibre and entails the degradation and removal of the axon and myelin from the distal stump. A similar degenerative process occurs as the final shared pathway contributing to most common neuropathies. MMP expression and localisation in the peripheral nervous system are compared with events in the CNS during Wallerian degeneration. Within 3 days after axotomy in the peripheral nervous system, MMP-9, MMP-7 and MMP-12 are elevated. These MMPs are produced by Schwann cells, endothelial cells and macrophages. The temporospatial expression of activated MMP-9 correlates with breakdown of the blood-nerve barrier. In the CNS, 1 week after optic nerve crush, four MMPs are induced and primarily localised to astrocytes, not microglia or oligodendrocytes. In the degenerating optic nerve, examined at later time points (4, 8, 12 and 18 weeks), MMP expression was down-regulated. The absence of MMPs in oligodendrocytes and mononuclear phagocytes during Wallerian degeneration may contribute to the slower removal of myelin debris observed in the CNS. The low level of the inactive pro-form of MMP-9 in the degenerating optic nerve may explain why the blood-brain barrier remains intact, while the blood-nerve barrier is rapidly broken down. We conclude that the difference in the level of expression, activation state and cellular distribution of MMPs may contribute to the different sequence of events observed during Wallerian degeneration in the peripheral compared to the CNS., (Copyright 2002 IBRO)

Purpose: To determine the intraoperative and postoperative complications and best-corrected visual acuity outcomes of eyes undergoing phacoemulsification and intraocular lens implantation after retinal detachment repair by the scleral buckling technique., Methods: The charts of all patients who underwent phacoemulsification and intraocular lens implantation between July 1991 and May 1998 in two surgical practices were reviewed to identify eyes with a history of retinal detachment repaired by the scleral buckling technique. Eyes with a history of pars plana vitrectomy were excluded. Demographic and surgical data, preoperative and postoperative best-corrected visual acuity, and intraoperative and postoperative complications were recorded., Results: We identified 34 eyes of 32 patients. The mean interval from retinal detachment repair to phacoemulsification was 12.4 years. The mean interval from phacoemulsification to final examination was 20 months. Risk factors for retinal detachment included isolated myopia (82%), myopia with lattice retinal degeneration (5.9%), and myopia with trauma (8.8%). One eye (2.9%) had no identifiable risk factors. Final best-corrected visual acuity of 20/40 or better was attained in 29 (85%) of 34 eyes and 20/20 or better in 18 (53%) of the eyes. Of the five eyes with the lowest best-corrected visual acuity, three had a macula-off retinal detachment; one had a posterior capsule opacity, epiretinal membrane, and corneal edema secondary to ocular ischemia; and one had advanced glaucoma. All five eyes still experienced an improvement in best-corrected visual acuity. With regard to complications, one eye had a posterior capsular tear with vitreous loss and another developed a postoperative retinal tear. Posterior capsule opacification requiring laser capsulotomy developed in 13 eyes (38%). No eye developed a retinal redetachment., Conclusion: Phacoemulsification and intraocular lens implantation can be performed safely after scleral buckling surgery and excellent best-corrected visual acuity results can be attained in most eyes. No modification of surgical technique is necessary. No retinal redetachment occurred in this series.

Purpose: We compared the changes in corneal astigmatism after phacoemulsification and intraocular lens implantation in 93 consecutive eyes with unsutured 4-mm superior scleral tunnel incisions to those through 105 consecutive eyes with unsutured 3.2- to 3.5-mm temporal corneal tunnel incisions., Methods: Keratometry measurements were obtained preoperatively and at postoperative day 1, week 1, and week 6. Group differences in scalar and vector astigmatism were compared by using analysis of variance methods., Results: Mean scalar astigmatism in the scleral incision group changed from preoperative astigmatism by 0.65 diopter at postoperative day 1, 0.37 diopter at postoperative week 1, and 0.13 diopter at postoperative week 6. Mean scalar astigmatism in the corneal incision group changed from preoperative astigmatism by 0.39 diopter at postoperative astigmatism by 0.39 diopter at postoperative day 1, 0.21 diopter at postoperative week 1, and 0.13 diopter at postoperative week 6. Mean vector astigmatism in the scleral incision group changed 1.26 diopters at 80 degrees at postoperative day 1, 1.05 diopters at 83 degrees at postoperative week 1, and 0.42 diopter at 103 degrees at postoperative week 6. Mean vector astigmatism in the corneal incision group changed 0.77 diopter at 90 degrees at postoperative week 1, and 0.61 diopter at 89 degrees at postoperative week 6. The differences were statistically significant (P = .003) only by vector analysis at the postoperative day 1 examination., Conclusions: We found significantly greater with-the-rule change in astigmatism in the scleral incision group than in the corneal incision group on the first postoperative day. The effect disappeared by the sixth postoperative week.

The biocompatibility of materials at an implant site involves a complex interaction of cells and tissues with the biomaterial. This cell-cell and cell-polymer interaction evokes the release of mediators such as chemotactic and growth factors that elicit and sustain inflammatory responses at the implant site. In this review, we summarize the interaction of cells with biomaterials in vitro and in vivo.

The biocompatibility of biomaterials at implant sites is controlled by the tissue/material interaction. A major cell in the tissue reaction is the macrophage. A summary is presented on macrophage mediation of cellular and humoral regulatory pathways in inflammatory and immune responses.

Macrophage activation following attachment to biomedical polymers was studied using two systems of analysis. Supernatants generated by human peripheral blood monocytes cultured on the surface of several different biomedical polymers were evaluated for the presence of the secreted regulatory protein interleukin 1 (IL1). In addition, each cell-polymer culture surface was subjected to scanning electron microscopy for gross morphological evaluation. Results indicate that, although all materials were efficient in the attachment and activation of cells, the panel of polymers showed a differential capacity in attachment and activation of monocytes. Dacron and polyethylene surfaces had a greater density of cells showing morphology indicative of activation, corresponding to elevated levels of IL1 in these cultures. Biomer and polydimethylsiloxane surfaces showed fewer activated cells and had lower IL1 levels in culture. Expanded polytetrafluorethylene resulted in intermediate levels of IL1 and attached cells showing activated morphology.