Abstract
Purpose: :
Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly people in the industrialized countries (1). Its most prominent pathologic features are lesions involving the retinal pigment epithelium (RPE) and Bruch’s membrane (BM), photoreceptor degeneration (2) and, in the most aggressive cases, choroidal neovascularization (CNV).CNV have been study in animal models by performing laser photocoagulation. Some of the features of human AMD have been observed in CCL2 -/CCR2 transgenic mouse models.Laser coagulation of the mouse choroid induces a local inflammatory reaction composed of blood-derived macrophages and activated MC (22).
Methods: :
We studied the influence of CX3CR1 deficiency in laser injury.
Results: :
Fourteen days after a laser injury, CX3CR1+/GFP mice showed some GFP-positive SrMC adjacent to the choroid scar but many more such cells had accumulated in the CX3CR1GFP/GFP mice at this stage. The cell counts after laser impact showed a transient increase in the CX3CR1+/GFP mice, peaking at day seven.At 14 days after the laser injury, there was significantly less CNV in CX3CR1+/+ mice than in their CX3CR1-/- counterparts. Quantification of the surface covered by the endothelial cells shows twice as much neovascularization in the two CX3CR1 (-/- and GFP/GFP) knockout strains than their controls.We analyzed the photoreceptor cell layer at 21 days. Photoreceptor cell layer thickness adjacent (200 µm) to the laser-induced retinal destruction did not differ significantly from that in the nonimpacted retina of CX3CR1+/+ mice. In contrast, under these conditions, the photoreceptor layer had thinned substantially in CX3CR1-/-mice. This difference may result from the combination of age- and laser-induced degeneration. To evaluate the laser-induced alteration, the relative retinal thicknesses of injured and uninjured retina were compared at different distances from the laser impact (ranging from 100 to 1000 µm). Laser-dependent retinal degeneration was significantly more pronounced in CX3CR1-/- mice at distances of 100 and 200 µm but not at 300 and 400 µm
Conclusions: :
CX3CR1KO mice showed an increased neovascular response after laser photocoagulation. this might be a physiopathogenic factor in choroidal neovascularization observed in human AMD.
Keywords: choroid: neovascularization • retinal glia