Role of Müller cells in cone mosaic rearrangement in a rat model of retinitis pigmentosa

Abstract

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 are organization 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 Müller 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 Müller 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-Müller-cell interactions mediate and maintain the rings. A test of this hypothesis can be performed by injecting DL-a-aminoadipic acid (AAA), which is known to disrupt Müller 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 Müller cells in RP. Thus, if the relationship between photoreceptors and Müller glia is better understood, the latter could potentially be manipulated for effective neuroprotection or the restoration of normal cone arrays.

Early remodeling of müller cells in the rd/rd mouse model of retinal dystrophy

“…Strettoi and co-workers proposed that neurons in retinal degeneration undergo dendritic pruning and later, sprouting due to loss of their afferent synapses (Strettoi and Pignatelli, 2000;Strettoi et al, 2002Strettoi et al, , 2003. This is supported by Lee et al (2011), who showed Müller cell processes remodel to match photoreceptor rearrangement in a rat model for retinitis pigmentosa. Altered glutamate signaling during retinal degeneration may also play an indirect role.…”

Taurine Depletion Causes ipRGC Loss and Increases Light-Induced Photoreceptor Degeneration

“…5,9 However, it is still unclear why the cone mosaic is reorganized into rings after photoreceptor loss. It has been suggested that cone rings could be the result of cone migration through processes of Müller cells 81 ; whereas other authors have proposed that it is due to cone death, 68 these studies indicated that rods die in the ''center of the rings'' and photoreceptor (cones and rods) loss expands outward, 27,68 suggesting an interdependence between neighboring photoreceptors. 82,83 Thus, it is likely that rings of cone degeneration could be the result of both cone death and migration.…”

Inhibition of Matrix Metalloproteinase 9 Enhances Rod Survival in the S334ter-line3 Retinitis Pigmentosa Model

“…After preliminary testing, 25 ug/ml was used throughout this study. The developmental stage for the injection of SB-3CT was either P15, when there was peak rod death [52] and formation of dying rod clusters [31, 32], or P40, when cone rings were observed throughout the retina [36]. One eye was injected with SB-3CT and the other eye was injected with PBS with 0.05–0.1% DMSO for comparison for each animal.…”