Role of Muller Cells in Cone Mosaic Rearrangement in a Rat Model of Retinitis Pigmentosa

Retinitis pigmentosa (RP) is a type of inherited retinal degenerative disease, which leads to blindness. The primary pathological event of this disease is the death of rods because of genetic mutations. The S334ter-line-3 rat is a transgenic model developed to express a rhodopsin mutation similar to that found in RP. In this study, the rod's death triggered a reorganization of the cone mosaic into an orderly array of rings. Four observations were relevant to understand this reorganization. First, rods died in hot spots, which progressively increased as circular waves, leaving rod-less zones behind. Second, rings of cones formed around these zones. Third, remodeled Muller glia processes enveloped cones and filled the center of their rings. Zonula occludens-1 located between the photoreceptor inner segments and the apical processes of Muller cells showed in the rings. Fourth, these rings were formed before the onset of cone cell deaths and were maintained until late stages of RP. From these observations, we hypothesize that cone-Muller-cell interactions mediate and maintain the rings. A test of this hypothesis can be performed by injecting DL-alpha-aminoadipic acid (AAA), which is known to disrupt Muller cell metabolism. A single intravitreal injection of AAA at P50 disrupted the rings of cones 3 days after the injection. These findings indicate that the rearrangement of cones in rings is modulated by Muller cells in RP. Thus, if the relationship between photoreceptors and Muller glia is better understood, the latter could potentially be manipulated for effective neuroprotection or the restoration of normal cone arrays. (C) 2011 Wiley-Liss, Inc.