Developmental Mechanisms Responsible for Differences in the Retinal Ganglion Cell Population Between Inbred Mouse Strains. R.C. Strom, R.W. Williams, and D. Goldowitz

We have found substantial strain variation in retinal ganglion cell number among inbred strains of mice. These differences may be caused by variation in cell production or cell death. To assess mechanisms producing these differences we have estimated the retinal ganglion cell population in mice from high and low retinal ganglion cell strains on their day of birth (P0), before the onset of naturally occurring ganglion cell loss in this species (Williams et al., 1990, EBR 82:393). Consequently, the total population at P0 provides a good estimate of total ganglion cell production. The ganglion cell population was estimated from electron microscopic analysis of axons in cross-sections of optic nerves. Four strains of mice were examined: two with high populations (BALB/c: 64,400 ± 2,000; DBA/2: 62,400 ± 1,100) and two with low populations (LP: 52,200 ± 1,900; C57BL/6: 53,900 ± 1,400) at maturity. At birth, a high strain, BALB/c has 236,991 ± 16,832 cells (n=4). In comparison, C57BL/6,a low strain, has 175,224 ± 12,300 cells (n=10). Thus, increased cell production in BALB/c relative to C57BL/6 can account for the adult differences. The decrease in number from P0 to maturity in both strains is approximately 70%. However, LP neonates had an average of 209,725 ± 21,725 (n=4) cells, well above the neonatal average of the C57BL/6 strain. In this strain 75% of cells die. In contrast, preliminary analysis of DBA/2 suggests that only 60% of the neonatal population is eliminated. These results indicate that some of the variation in cell number at P0 is due to differences in the kinetics or timing of ganglion cell production. In, conclusion, the differences in the size of the ganglion cell population at maturity in strains is probably due to a combination of differences in both neuron production and loss.