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Survival and Long Distance Migration of Brain-Derived Precursor Cells Transplanted to Adult Rat Retina

^a Wallenberg Retina Center, Department of Ophthalmology, Lund University Hospital;
^b Wallenberg Neuroscience Center, Department of Physiological Sciences, Lund University, Lund, Sweden

Key Words. Brain-derived precursor cells • RN33B • Subretinal transplantation • Cell markers • Whole-mounted retina • Migration

Anita Blixt Wojciechowski, M.D., Department of Ophthalmology, Lund University Hospital, S-221 84 Lund, Sweden. Telephone: 46-46-2220769; Fax: 46-46-2220774; e-mail: a.blixt{at}bredband.net or anita.blixt_wojciechowski{at}oft.lu.se

Neural precursor cells transplanted to adult retina can integrate into the host. This is especially true when the neural precursor rat cell line RN33B is used. This cell line carries the reporter genes LacZ and green fluorescent protein (GFP). In grafted rat eyes, RN33B cells are localized from one eccentricity to the other of the host retina. In the present study, whole-mounted retinas were analyzed to obtain a more appropriate evaluation of the amount of transgene-expressing cells and the migratory capacity of these cells 3 and 8 weeks post-transplantation. Quantification was made of the number of ß-galactosidase- and GFP-expressing cells with a semiautomatized stereological cell counting system. With the same system, delineation of the distribution area of the grafted cells was also performed. At 3 weeks, 68% of the grafted eyes contained marker-expressing cells, whereas at 8 weeks only 35% of the eyes contained such cells. Counting of marker-expressing cells demonstrated a lower number of transgene-expressing cells at 3 weeks compared with 8 weeks post-transplantation. The distribution pattern of marker gene-expressing cells revealed cells occupying up to 21% at 3 weeks and up to 68% at 8 weeks of the entire host retina post-grafting. The precursor cells survived well in the adult retina although the most striking feature of the RN33B cell line was its extraordinary migratory capacity. This capability could be useful if precursor cells are used to deliver necessary genes or gene products that need to be distributed over a large diseased area.

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