Abstract
Purpose :
Cd9 (MRP-1) is one of tetraspanin membrane proteins, and plays various roles in tissue development and disease pathogenesis, especially in cancer, but the expression patterns and function of Cd9 in retinal development are not well understood. In this study, we first aimed to reveal the spatial and temporal expression patterns of Cd9 in developing and mature mouse retina. Furthermore, its expression in the pathological condition of retina. We also asked the roles of Cd9 in retinal development and degeneration.
Methods :
The expression pattern of Cd9 during retinal development and degeneration was examined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. The function of Cd9 during retinal development and degeneration was examined by the Cd9-knockout mice. (Cd9-knockout) As photoreceptor degeneration models, Rd1 mouse and chemical induction of degeneration by MNU and NaIO3 were employed.
Results :
Cd9 transcripts were only weakly expressed in the retina at E14, but its expression level subsequently increased and peaked at around P12. In adult retina, mRNA expression decreased slightly but was maintained at a significant level. RNA-seq of fractionated ertinal cells and immunohistochemistry indicated that Cd9 was expressed abundantly in Mueller glia and weakly in other retinal cells. Interestingly, when photoreceptors were damaged, Cd9 expression was drastically increased in rod photoreceptors and decreased in Mueller glia. Morphological examination suggested that Cd9-knockout mouse retina developed normally. However, once the photoreceptor degeneration started, pathology of rod was more severe in Cd9-knockout retina than control. Induction of cytokines, which are known to be protective to photoreceptor damage, was hampered in Cd9-knockout retina.
Conclusions :
Taken together, although Cd9 is dispensable for normal development, it plays roles to protect rod photoreceptors.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.