Long-term reconstruction of foveal microstructure and visual acuity after idiopathic macular hole repair: three-year follow-up study

AimsTo evaluate long-term reconstructive changes in foveal microstructures and their associations with visual improvement in eyes with surgically closed macular holes (MHs).MethodsTwenty-eight eyes of 28 patients who underwent successful idiopathic MH repair were retrospectively studied. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography images were examined preoperatively and 1, 3, 6, 12, 24 and 36 months postoperatively. Correlations between postoperative BCVA and parameters relating to the reconstruction of the foveal photoreceptor layer including the external limiting membrane (ELM), ellipsoid zone (EZ) and cone interdigitation zone (CIZ) as well as changes in glial cells were evaluated.ResultsLogarithm of the minimum angle of resolution BCVA improved continuously during 3-year follow-up (baseline 0.70±0.27, 1 month 0.36±0.34, 3 months 0.29±0.30, 6 months 0.22±0.24, 12 months 0.18±0.25, 24 months 0.14±0.22, 36 months 0.10±0.19) (p=0.015). Continuous reconstruction of the foveal microstructure was apparent throughout the 3-year follow-up. The reconstruction process was initiated by glial proliferation, followed by ELM bridging, glial elimination with EZ reconstruction and CIZ reconstruction. Better BCVA at the 3-year time-point was significantly associated with early ELM bridging, early glial disappearance and photoreceptor integrity defined as complete reconstruction of the ELM, EZ and CIZ.ConclusionsIntegrity of the photoreceptor layer was correlated with better long-term visual outcomes after MH repair. Reconstruction of the foveal ELM and disappearance of glial proliferation in the early postoperative period predicted better visual recovery.

Molecular mechanism of central nervous system repair by the Drosophila NG2 homologue kon-tiki

Neuron glia antigen 2 (NG2)–positive glia are repair cells that proliferate upon central nervous system (CNS) damage, promoting functional recovery. However, repair is limited because of the failure of the newly produced glial cells to differentiate. It is a key goal to discover how to regulate NG2 to enable glial proliferation and differentiation conducive to repair. Drosophila has an NG2 homologue called kon-tiki (kon), of unknown CNS function. We show that kon promotes repair and identify the underlying mechanism. Crush injury up-regulates kon expression downstream of Notch. Kon in turn induces glial proliferation and initiates glial differentiation by activating glial genes and prospero (pros). Two negative feedback loops with Notch and Pros allow Kon to drive the homeostatic regulation required for repair. By modulating Kon levels in glia, we could prevent or promote CNS repair. Thus, the functional links between Kon, Notch, and Pros are essential for, and can drive, repair. Analogous mechanisms could promote CNS repair in mammals.