title: 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.
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, California 90089-1111, USA. eunjinl@bmsr.usc.edu
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Lee
authors.forename: Yerina
authors.initials: Y
authors.lastname: Ji
authors.forename: Colleen L
authors.initials: CL
authors.lastname: Zhu
authors.forename: Norberto M
authors.initials: NM
authors.lastname: Grzywacz
mesh_terms: D015074:2-Aminoadipic Acid / Q000008:administration & dosage; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D058449:Intravitreal Injections; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D009154:Mutation / Q000235:genetics; D009457:Neuroglia / Q000502:physiology*; D055355:Opsins / Q000235:genetics; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology; D012174:Retinitis Pigmentosa / Q000473:pathology* / Q000503:physiopathology; D012243:Rhodopsin / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
chemical_list: D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D055355:Opsins; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D015074:2-Aminoadipic Acid; D012243:Rhodopsin; D005974:Glutamate-Ammonia Ligase