LINEAGE STUDY OF DEGENERATING PHOTORECEPTOR CELLS IN THE RD MOUSE RETINA

Purpose. A retroviral marker was used to label daughter cells arising from individual neuroblasts in the rd mouse retina, in order to invest igate the hypothesis that a clonal relationship exists among degenerat ing photoreceptor cells.Methods. On the day of birth, a single injecti on of retrovirus with a lac Z (beta-galactosidase) reporter construct was injected into the retina in the vicinity of the subretinal space. Descendants of single neuroblasts were identified histochemically by e xamining the retinas at P14 (postnatal day 14). Light and electron mic roscopic studies were used to identify the retrovirally-induced marker beta-D-galactosidase using Blue-gal dye. Double-labeling of degenerat ing cone cells was accomplished by taking 100 mu m vibratome sections of retrovirally-injected eyes and using either FITC-PNA or HRP-PNA to visualize clusters of degenerating cones as well as Blue-gal labeled c lones of photoreceptor cells on the same tissue section. Results. A re latively large number of clones of primarily photoreceptor cells were observed in the peripheral retinas of both normal and rd mice. In a fe w cases in the rd, photoreceptor cells in a given clone consisted of b oth PNA- and Blue-gal-labeled cells as well as of only Blue-gal-labele d cells. Conclusion. These results suggest that during the period of i ntense cell death in the rd retina, a single dying photoreceptor cell can be surrounded by photoreceptors (either rods or cones) from the sa me clone that appear morphologically normal with out evidence of degen eration.