Slit1b-Robo3 signaling and N-cadherin regulate apical process retraction in developing retinal ganglion cells.

When neurons exit the cell cycle after their terminal mitosis, they detach from the apical surface of the neuroepithelium. Despite the fact that this detachment is crucial for further neurogenesis and neuronal migration, the underlying mechanisms are still not understood. Here, taking advantage of the genetics and imaging possibilities of the zebrafish retina as a model system, we show by knockdown experiments that the guidance molecule Slit1b and its receptor Robo3 are required for apical retraction of retinal ganglion cells (RGCs). In contrast, N-cadherin seems to be responsible for maintenance of apical attachment, as expression of dominant-negative N-cadherin causes RGCs to lose apical attachments prematurely and rescues retraction in slit1b morphants. These results suggest that Slit-Robo signaling downregulates N-cadherin activity to allow apical retraction in newly generated RGCs.

Toward robot-assisted vascular microsurgery in the retina.

BACKGROUND: Experimental protocol in our laboratory routinely requires the precise placement of instruments at, or near, the retina. Although manipulators for placing an instrument within the eye presently exist, none of the designs were satisfactory due to limitations on size, accuracy and operability. To overcome these limitations, we have developed a novel six degree of freedom manipulator designed specifically for retinal microsurgery. METHODS: The manipulator is parallel in structure and provides submicrometer positioning of an instrument within the constrained environment of the eye. The position of an instrument attached to the manipulator is commanded by the operator using a hand-held trackball. A computer controller interprets the trackball input and moves the manipulator in an intuitive manner according to mathematically constrained modes of operation. RESULTS: Over 50 retinal vessels in the live, anesthetized cat have been successfully cannulated for pressure measurement and drug injection using the described manipulator and micropuncture techniques. The targeted vessels ranged in internal diameter from 20 to 130 microns. CONCLUSION: This device has applications in microsurgery where tremor and fatigue limit the performance of an unaided hand and where mechanically constrained manipulators are inappropriate due to size and operative constraints.