Abstract
Purpose:
It has been previously shown that chemokine signaling is essential for normal central nervous system function and maintenance. The function(s) of the β-chemokine CCL5 in normal murine retina are not well elucidated. Thus in this study, we examined the potential relevance of CCL5 signaling to visual function and maintenance in healthy retina.
Methods:
We performed visual evoked potentials (VEPs) to assess global visual function in normal, wild-type C57 and Ccl5-/- mice (4 month) and quantified N1 and P1 amplitudes and latencies. Additionally, we measured retinal thickness using optical coherence tomography, as well as assessed ganglion cell (GC) axon number and anterograde transport function in C57 and Ccl5-/- mice. Using immunohistochemistry and quantitative digital microscopy, we quantified total cell numbers of rod bipolar, amacrine and horizontal cells in longitudinal paraffin sections of C57 and Ccl5-/- retina.
Results:
Using VEPs, Ccl5-/- mice show a statistically significant difference in N1 amplitude (40.82µV vs. 58.24µV; p=0.012), but not N1 latency (53.67ms vs. 52.31ms; p=0.421) compared to C57 mice. Ccl5-/- mice exhibit no difference in P1 amplitude (41.36µV vs. 48.88µV; p=0.182), despite a significant delay in P1 latency (115.64ms vs. 89.59ms; p<0.001), compared to C57 mice. In healthy retina, Ccl5-/- mice display a statistically significant reduction of inner plexiform (IPL; p<0.001) and inner nuclear layer thickness (INL; p=0.16), while other layers remained unchanged compared to C57 retina. With respect to GC axon counts, Ccl5-/- mice show no significant difference in GC axon density compared to C57 mice (p=0.894). Furthermore, Ccl5-/- GCs retain their functional capacity to transport fluorescently-labeled cholera toxin β to the superior colliculus. Despite a paucity of alterations in GC axon numbers in Ccl5-/- retina, there are greater numbers of syntaxin+ amacrine cells (p<0.001) in the INL, but no quantifiable changes in calbindin+ horizontal cells or PKCα+ rod bipolar cells compared to healthy C57 retina.
Conclusions:
These data support a novel functional role for constitutive CCL5 signaling in healthy retina and provide evidence that CCL5 may be relevant to the development or maintenance of lateral inhibition in the inner retina via amacrine cells. Moreover, CCL5 signaling in healthy retina may be critical for normal visual function and homeostasis of retinal function and circuitry.
Keywords: 531 ganglion cells •
490 cytokines/chemokines •
691 retina: proximal (bipolar, amacrine, and ganglion cells)