Biomechanical stress in the retinal pigment epithelium surrounding laser scars in humans
Purpose : The wound response of an epithelium comprises tissue-scale activation of stress fibers whose contraction regionally reconfigures the epithelium and drives closure of the wound. Recent in vitro studies have shown that similar biomechanical processes can paradoxically lead to enlargement of epithelial holes. In patients having undergone laser photocoagulation of the retinal pigment epithelium (RPE), laser scars may expand over years. Here, to document the implication of epithelial biomechanics in the enlargement of laser scars we analyzed the dynamic changes affecting the RPE around scars in patients and performed confocal microscopy on a RPE flat-mount from a donor eye. Methods: We analyzed the image files of five patients (age 61 to 85 years) showing enlargement of laser scars in the RPE (follow-up, 13 to 60 months). In three of them, prospective imaging was performed using transscleral illumination adaptive optics ophthalmoscopy (AOO), an imaging technology enabling visualization of RPE cells. Time-lapse sequences were analyzed to track dynamic processes in the RPE surrounding scars. A flat-mounted phalloidin-labeled RPE from a human donor eye with a history of scatter photocoagulation was examined by confocal microscopy to document the distribution of stress fibers and cell metrics. Results: Time-lapse sequences showed that enlargement of laser scars was accompanied by the displacement of microscopic features in margins of atrophy. AOO imaging suggested locally coordinated displacement of mosaic of darks spots, with a generally radial or tangent direction relative to the edges of scars. Such movements were detected up to several hundred microns from the edges of scars. On the histology sample, elongated RPE cells with stress fibers forming actin cables were found along edges of scars, which formed fascicles between adjacent scars. Conclusion: Enlargement of RPE scars may be accompanied by long-lasting, largescale changes in the distribution of microscopic features in the margins of lesions. In particular, transscleral illumination AOO showed coordinated displacement of a mosaic similar to the one described for the RPE. The finding by histology of RPE cell with a tractional phenotype along edges further suggests that epithelial biomechanics contribute to such movements and may hence contribute to scar enlargement.