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Reshaping the Cone-Mosaic in a Rat Model of Retinitis Pigmentosa: Modulatory Role of ZO-1 Expression in DL-Alpha-Aminoadipic Acid Reshaping
- Title
- Reshaping the Cone-Mosaic in a Rat Model of Retinitis Pigmentosa: Modulatory Role of ZO-1 Expression in DL-Alpha-Aminoadipic Acid Reshaping
- Authors
- Yu, Wan-Qing; Eom, Yun Sung; Shin, Jung-A; Nair, Divya; Grzywacz, Sara X. Z.; Grzywacz, Norberto M.; Craft, Cheryl Mae; Lee, Eun-Jin
- Ewha Authors
- 신정아
- SCOPUS Author ID
- 신정아
- Issue Date
- 2016
- Journal Title
- PLOS ONE
- ISSN
- 1932-6203
- Citation
- PLOS ONE vol. 11, no. 3
- Publisher
- PUBLIC LIBRARY SCIENCE
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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 Muller 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 Muller 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 Muller 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.
- DOI
- 10.1371/journal.pone.0151668
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
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