June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
The role of Tet3 in retinal development and function
Author Affiliations & Notes
  • Grazia Giorgio
    Department of Ophthalmology, Ludwig-Maximilians-Universitat Munchen, Munchen, Bayern, Germany
    Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universitat Munchen, Planegg, Bayern, Germany
  • Silke Haverkamp
    Department of Computational Neuroethology, Stiftung caesar, Bonn, Nordrhein-Westfalen, Germany
  • Elisa Murenu
    Department of Ophthalmology, Ludwig-Maximilians-Universitat Munchen, Munchen, Bayern, Germany
  • Stylianos Michalakis
    Department of Ophthalmology, Ludwig-Maximilians-Universitat Munchen, Munchen, Bayern, Germany
    Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universitat Munchen, Planegg, Bayern, Germany
  • Footnotes
    Commercial Relationships   Grazia Giorgio None; Silke Haverkamp None; Elisa Murenu None; Stylianos Michalakis None
  • Footnotes
    Support  International Research Training Groups (IRTG), SFB1309
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4283. doi:
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      Grazia Giorgio, Silke Haverkamp, Elisa Murenu, Stylianos Michalakis; The role of Tet3 in retinal development and function. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4283.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Tet3 is a member of the ten-eleven translocation enzymes, which include also Tet1 and Tet2. Their canonical function is the oxidation of the 5-methylcytocine (5mC) on the DNA into 5-hydroximethylcytosine (5hmC), and subsequent oxidative states, thereby promoting increased gene expression. Tet3 is expressed in the mouse retina from early postnatal stages, implying its role during the same time window in which retina cells develop and mature. Although Tet3 is the most abundant member in brain and retina, its role in the latter has not been addressed.

Methods : Mutations in the Tet3 catalytic domain has been previously identified and linked to neurological, but also ophthalmological defects. Using a Rax-Cre driver line and a Tet3 floxed mouse, we generated conditional mutant (cMut) mice lacking part of the Tet3 catalytic domain in retinal progenitors and their progeny. Mice have been characterized using a variety of techniques ranging from immunohistochemistry with cell specific markers, ultrastructural analysis of cell morphology by electron microscopy (EM) and electroretinography (ERG) to assess retinal functionality.

Results : Cone photoreceptors, responsible for diurnal and color vision, are of two subtypes in the mouse retina. S-cones, sensitive to blue light, have an increasing dorsal to ventral gradient. M-cones, responsive to green light, are more evenly distributed, although less abundant in the ventral part. Except for the dorsal retina with a prevalence of M-cones, many cones are hybrid and express both S and M photopigments. Preliminary results show that cMut mice have an increased number of cones and altered cone subtype distribution. In fact, S opsin-positive cones are higher in numbers and lack the characteristic dorsal to ventral gradient. As a consequence, all the cones of Tet3 mutant mice appear to be hybrid. The increased cone number is accompanied by a reduction in the total cell number of the inner nuclear layer affecting the functionality of the retina and the propagation of the light stimulus as shown by ERG b-wave measurements. This altered functionality seems not be linked to missing or defective synaptic components as revealed by EM analysis.

Conclusions : These results suggest that Tet3 has a selective role in retinal development and/or lineage specification. Elucidating the mechanisms downstream of Tet3 will improve our understanding of retinal homeostasis under physiological and pathophysiological conditions.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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