Assessment of Retinal Function and Morphology in Aging Ccl2 Knockout Mice

Abstract

<p><b>PURPOSE.</b> The chemokine Ccl2, or monocyte chemoattractant protein-1 (MCP-1), has previously been identified as playing a potential role in many ocular diseases" however, its role in mice is less clear. We sought to correlate changes in retinal pigment epithelium (RPE) and retinal morphology with changes in function in aging Ccl2/ mice.</p> <p><b>METHODS.</b> Ccl2^-/- mice on a C57BL6J background were genotyped for <i>Crb1^rd8/rd8,</i> and were free of this mutation. Ccl2^-/- mice and wild-type (WT) C57BL6J mice were investigated for changes in the retinal fundus and histology as a function of age. The function of the rod and cone pathways, and the rate of dark adaptation, was assessed using the electroretinogram (ERG) up to 15 months of age.</p> <p><b>RESULTS.</b> Fifteen-month-old Ccl2^-/- mice had fundus lesions, more subretinal microglia/ macrophages, and an increase in RPE cell size, indicative of RPE cell loss, when compared with WT mice. Within the retina, gross morphology was normal but there was an increase in Muller cell gliosis and microglial activation. These morphological changes in the Ccl2^-/- RPE/ retina did not correlate with a change in either rod or cone ERG pathway function, or with the rate of dark adaptation.</p> <p><b>CONCLUSIONS.</b> These data show that Ccl2 is important for preserving RPE and glial morphology with age, yet retinal function and gross morphology are maintained. Altered signaling in this chemokine pathway may, however, increase RPE and retinal vulnerability to disease.</p>