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Ivan Conte, Sandro Banfi, Enrico Maria Surace, Sabrina Asteriti, Lorenzo Cangiano, Elena Marrocco, Mariateresa Pizzo, Sara Barbato, Danila Falanga, Daniela Intartaglia, Federica Naso; mir-204/211 in RPE/photoreceptor crosstalk: an intricate relationship. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4535.
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© ARVO (1962-2015); The Authors (2016-present)
In last decade, the microRNAs (miRNAs) are emerging as key players in the control of fundamental biological processes. We recently identified miR-204/211 miRNA family as new “key regulator” of vertebrate eye development. We demonstrated their role in eye morphogenesis including lens formation and dorso-ventral patterning of the retina. We also showed their contribution in the control of axon guidance of retinal ganglion cells and we identified a dominant mutation in miR-204 as the genetic cause of a unique phenotype of photoreceptor degeneration and coloboma. While the role of miR-204/211 in eye development has been characterized, the relationship occurring between their function and photoreceptor development and function is still not completely characterized. To gain insights in this direction, here, we focus on the in vivo role of both miR-204 and miR-211, in both mammalian and teleost models.
Both miR-204 and miR-211 in RPE/Photoreceptor crosstalk was assessed by genetic deletion, which specifically eliminated the precursor sequence of miR-204 and miR-211 from the medaka and mouse genome, respectively. Analysis of eye phenotypes has included morphological inspection and detection of modification in the expression of retina markers by in situ hybridization experiments. Immunohistochemistry was also used to detect cell type, proliferation, and cell programmed death markers in the adult retina.
We found that deletion of miR-204 and miR-211 in mouse and medaka fish, respectively, resulted in specific eye phenotype, which revealed a progressive photoreceptor cell degeneration characterized by an impaired electroretinogram (ERG) response to light stimuli. Additionally, our data demonstrate that the effects of miR-204 over-expression in photoreceptor cells of medaka fish also promote opposite changes in the levels of expression of photoreceptor cell specific markers
Taken together, these results not only allow us to gain a comprehensive understanding of miR-204/211 function and dysfunction but also established the existence of precise network between miR-204/211 function and the RPE/photoreceptor crosstalk opening new perspective for the use of this knowledge to develop novel therapeutic strategies to treat inherited retinal dystrophies
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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