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Intravitreous transplantation of encapsulated fibroblasts secreting the human fibroblast growth factor 2 delays photoreceptor cell degeneration in Royal College of Surgeons rats.

ABSTRACT: We developed an experimental approach with genetically engineered and encapsulated mouse NIH 3T3 fibroblasts to delay the progressive degeneration of photoreceptor cells in dark-eyed Royal College of Surgeons rats. These xenogeneic fibroblasts can survive in 1. 5-mm-long microcapsules made of the biocompatible polymer AN69 for at least 90 days under in vitro and in vivo conditions because of their stable transfection with the gene for the 18-kDa form of the human basic fibroblast growth factor (hFGF-2). Furthermore, when transferred surgically into the vitreous cavity of 21-day-old Royal College of Surgeons rats, the microencapsulated hFGF-2-secreting fibroblasts provoked a local delay of photoreceptor cell degeneration, as seen at 45 days and 90 days after transplantation. This effect was limited to 2.08 mm2 (45 days) and 0.95 mm2 (90 days) of the retinal surface. In both untreated eyes and control globes with encapsulated hFGF-2-deficient fibroblasts, the rescued area (of at most 0.08 mm2) was significantly smaller at both time points. Although, in a few ocular globes, surgical trauma induced a reorganization of the retinal cytoarchitecture, neither microcapsule rejection nor hFGF-2-mediated tumor formation were detected in any treated eyes. These findings indicate that encapsulated fibroblasts secreting hFGF-2 or perhaps other agents can be applied as potential therapeutic tools to treat retinal dystrophies.

SUBMITTER: Uteza Y

PROVIDER: S-EPMC15906 | biostudies-literature | 1999 Mar

REPOSITORIES: biostudies-literature

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Intravitreous transplantation of encapsulated fibroblasts secreting the human fibroblast growth factor 2 delays photoreceptor cell degeneration in Royal College of Surgeons rats.

Uteza Y Y Rouillot J S JS Kobetz A A Marchant D D Pecqueur S S Arnaud E E Prats H H Honiger J J Dufier J L JL Abitbol M M Neuner-Jehle M M

Proceedings of the National Academy of Sciences of the United States of America 19990301 6

We developed an experimental approach with genetically engineered and encapsulated mouse NIH 3T3 fibroblasts to delay the progressive degeneration of photoreceptor cells in dark-eyed Royal College of Surgeons rats. These xenogeneic fibroblasts can survive in 1. 5-mm-long microcapsules made of the biocompatible polymer AN69 for at least 90 days under in vitro and in vivo conditions because of their stable transfection with the gene for the 18-kDa form of the human basic fibroblast growth factor ( ...[more]

PMID: 10077648

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Project description:Prior structural studies of posterior subcapsular cataract (PSC) development in Royal College of Surgeons (RCS) rats suggest that migration of basal fiber ends was disrupted, ultimately resulting in a PSC. Therefore the goal of this study was to assess the overall migration patterns as well as changes to the structure and cytoskeleton of basal fiber ends during PSC development.Lenses from 48 RCS dystrophic rats (RCS/Lav) and 24 genetically matched control animals (RCS-rdy(+)/Lav) from 2 to 8 weeks old were examined. Equatorial diameters were measured and suture patterns were photographed immediately following enucleation/dissection. Right eye lenses were fixed and processed to visualize the actin cytoskeleton via laser scanning confocal microscopy (LSCM), left eye lenses were decapsulated, fixed and processed for scanning electron microscopy (SEM). Scaled 3D-computer assisted drawings (CADs) and animations were constructed from the data to depict the changes in suture patterns and fiber end architecture.At 2 weeks, dystrophic lenses displayed an inverted Y suture on the posterior, and by 3 weeks most lenses had at least one sub-branch. Additional sub-branches were observed with time, opacities being visible as early as 4 weeks and progressing into PSC plaques by 6 weeks. Control lenses displayed inverted Y sutures at all ages and were transparent. SEM of dystrophic lenses revealed fiber ends with normal size, shape, arrangement, and filopodia at 2 weeks; scattered areas of dome-shaped fiber ends and small filopodia were present at 3 weeks. At 4 weeks the irregularly arranged domed fiber ends had extremely long filopodia with 'boutons' at their tips. By 6 weeks all fiber ends within plaques displayed rounded or domed basal membranes and lacked filopodial extensions. Control lenses at all time points had comparable ultrastructure to the 2 week old dystrophic lenses. F-actin arrangement within the basal membrane complex (BMC) of control lenses showed the expected peripheral pattern of labeling at all ages. Dystrophic RCS lenses at 2 weeks were comparable to controls, however by 3-4 weeks they displayed scattered foci of F-actin within the BMC. At all time points thereafter, F-actin was rearranged into a 'rosette' pattern of prominent foci at cell vertices.The data are consistent with the hypothesis that migration of basal fiber ends is altered in a two stage process wherein initially, migration patterns undergo a rapid shift resulting in abnormal suture sub-branch formation. Subsequent cytological alterations are consistent with an eventual cessation of migration, precluding proper targeting of basal ends to their sutural destinations and leading to cataract plaque formation.

Project description:The scale of the COVID-19 pandemic means that a significant number of patients who have previously been infected with SARS-CoV-2 will require surgery. Given the potential for multisystem involvement, timing of surgery needs to be carefully considered to plan for safe surgery. This consensus statement uses evidence from a systematic review and expert opinion to highlight key principles in the timing of surgery. Shared decision-making regarding timing of surgery after SARS-CoV-2 infection must account for severity of the initial infection; ongoing symptoms of COVID-19; comorbid and functional status; clinical priority and risk of disease progression; and complexity of surgery. For the protection of staff, other patients and the public, planned surgery should not be considered during the period that a patient may be infectious. Precautions should be undertaken to prevent pre- and peri-operative infection, especially in higher risk patients. Elective surgery should not be scheduled within 7 weeks of a diagnosis of SARS-CoV-2 infection unless the risks of deferring surgery outweigh the risk of postoperative morbidity or mortality associated with COVID-19. SARS-CoV-2 causes either transient or asymptomatic disease for most patients, who require no additional precautions beyond a 7-week delay, but those who have persistent symptoms or have been hospitalised require special attention. Patients with persistent symptoms of COVID-19 are at increased risk of postoperative morbidity and mortality even after 7 weeks. The time before surgery should be used for functional assessment, prehabilitation and multidisciplinary optimisation. Vaccination several weeks before surgery will reduce risk to patients and might lessen the risk of nosocomial SARS-CoV-2 infection of other patients and staff. National vaccine committees should consider whether such patients can be prioritised for vaccination. As further data emerge, these recommendations may need to be revised, but the principles presented should be considered to ensure safety of patients, the public and staff.

Dataset Information

Intravitreous transplantation of encapsulated fibroblasts secreting the human fibroblast growth factor 2 delays photoreceptor cell degeneration in Royal College of Surgeons rats.

Publications

Intravitreous transplantation of encapsulated fibroblasts secreting the human fibroblast growth factor 2 delays photoreceptor cell degeneration in Royal College of Surgeons rats.

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