title: Reshaping the Cone-Mosaic in a Rat Model of Retinitis Pigmentosa: Modulatory Role of ZO-1 Expression in DL-Alpha-Aminoadipic Acid Reshaping.
abstract: In S334ter-line-3 rat model of Retinitis Pigmentosa (RP), rod cell death induces the rearrangement of cones into mosaics of rings while the fibrotic processes of Müller cells remodel to fill the center of the rings. In contrast, previous work established that DL-alpha-aminoadipic-acid (AAA), a compound that transiently blocks Müller cell metabolism, abolishes these highly structured cone rings. Simultaneously, adherens-junction associated protein, Zonula occludens-1 (ZO-1) expression forms in a network between the photoreceptor segments and Müller cells processes. Thus, we hypothesized that AAA treatment alters the cone mosaic rings by disrupting the distal sealing formed by these fibrotic processes, either directly or indirectly, by down regulating the expression of ZO-1. Therefore, we examined these processes and ZO-1 expression at the outer retina after intravitreal injection of AAA and observed that AAA treatment transiently disrupts the distal glial sealing in RP retina, plus induces cones in rings to become more homogeneous. Moreover, ZO-1 expression is actively suppressed after 3 days of AAA treatment, which coincided with cone ring disruption. Similar modifications of glial sealing and cone distribution were observed after injection of siRNA to inhibit ZO-1 expression. These findings support our hypothesis and provide additional information about the critical role played by ZO-1 in glial sealing and shaping the ring mosaic in RP retina. These studies represent important advancements in the understanding of retinal degeneration's etiology and pathophysiology.
authors.affiliation: Neuroscience Graduate Program, University of Southern California, Los Angeles, California, United States of America.|Department of Biological Structure, University of Washington, Seattle, United States of America.
authors.forename: Wan-Qing
authors.initials: WQ
authors.lastname: Yu
authors.affiliation: Mary D. Allen Laboratory for Vision Research, USC Eye Institute, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Yun Sung
authors.initials: YS
authors.lastname: Eom
authors.affiliation: Mary D. Allen Laboratory for Vision Research, USC Eye Institute, University of Southern California, Los Angeles, California, United States of America.|Department of Anatomy, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Jung-A
authors.initials: JA
authors.lastname: Shin
authors.affiliation: Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Divya
authors.initials: D
authors.lastname: Nair
authors.affiliation: Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Sara X Z
authors.initials: SX
authors.lastname: Grzywacz
authors.affiliation: Neuroscience Graduate Program, University of Southern California, Los Angeles, California, United States of America.|Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, California, United States of America.|Department of Neuroscience, Georgetown University, Washington D.C., United States of America.|Department of Physics, Georgetown University, Washington D.C., United States of America.
authors.forename: Norberto M
authors.initials: NM
authors.lastname: Grzywacz
authors.affiliation: Neuroscience Graduate Program, University of Southern California, Los Angeles, California, United States of America.|Mary D. Allen Laboratory for Vision Research, USC Eye Institute, University of Southern California, Los Angeles, California, United States of America.|Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.|Department of Cell & Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Cheryl Mae
authors.initials: CM
authors.lastname: Craft
authors.affiliation: Mary D. Allen Laboratory for Vision Research, USC Eye Institute, University of Southern California, Los Angeles, California, United States of America.|Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, California, United States of America.|Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Lee
mesh_terms: D015074:2-Aminoadipic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D063928:Ependymoglial Cells / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005355:Fibrosis; D007382:Intermediate Filaments / Q000378:metabolism; D058449:Intravitreal Injections; D008297:Male; D055355:Opsins / Q000172:deficiency / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000473:pathology / Q000503:physiopathology*; D019076:Transgenes; D062826:Zonula Occludens-1 Protein / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D055355:Opsins; D034741:RNA, Small Interfering; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D015074:2-Aminoadipic Acid