In collaboration with Martin L. Katz and Mark D. Kirk, I tested whether retinal degeneration could be slowed in a mouse model of Batten disease. Undifferentiated embryonic stem cells were maintained using LIF (leukemia inhibitory factor). Four days after removal of LIF from the culture medium, the cells were treated with retinoic acid for 4 days to induce differentiation into neural precursors, balls of cells called embryoid bodies. Cells expressed neural markers like beta tubulin. After these neural precursors were injected into the eye, many migrated to the inner limiting membrane, but some of the transplanted cells could be found in the inner plexiform layer of the neural retina, as revealed by GFP (green fluorescent protein). Charles Thomas (at LOCI) and I used confocal microscopy to construct z-focus animations showing details (processes, nuclei, etc.) of such GFP-labeled neurons in the retina. Note the striking elaboration of neuronal morphology. For a 6 week old mnd (motor neuron degeneration) mouse, (the model of Batten disease, a mutation of Cln8), I found a greatly reduced ERG (middle trace) relative to a black control mouse (top trace) to a brief but intense flash (bottom trace). Black controls have a healthy ERG as judged from the V-logI (micro Volts as a function of log quanta per sq cm per s); it is well-known that the b-wave reaches saturation at lower intensity than the a- and c-waves. We found a mnd mouse in which there appeared to be significant rescue from the loss of ERG retinal sensitivity when stem cells had been previously injected into the anesthetized animal's eye.


An abstract on this work:

Stark, W. S., Katz, M. L., Meyer, J. S., Agarwal, S., Kirk, M. D. Transplantation of stem
cell-derived neural precursors into the eyes of mice with hereditary retinal degeneration, Association for Research in Vision and Ophthalmology, 2002, Fort Lauderdale, FL (*Investigative Ophthalmology and Visual Science, 2002, 43). Abstract on line


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