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Sarah Decembrini, Botond Roska, Martin Biel, Yvan Arsenijevic; Characterization of a cone-specific mouse transgenic line and subsequent cone transplantation in a mouse model of cone-rod dystrophy.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5479.
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© ARVO (1962-2015); The Authors (2016-present)
Cone-rod dystrophies, affecting 1 in 40’000 people, are inherited retinal dystrophies leading to the loss of central, daylight and color vision due to primary cone photoreceptor degeneration. Noteworthy, rod dystrophies due to a specific rod gene mutation are often followed by cone loss. Because the human vision relies mostly on cone-mediated vision it is of prime importance to replace cones in degenerated retinas.
Here, we describe the characterization of a new transgenic mouse line, namely the Chrnb4-EGFP line, expressing the reporter gene exclusively in mature Gnat2- OPN1MW/LW- OPN1SW- positive cones of adult retinas.
At early embryonic (E) stages, the EGFP co-localized with retinal progenitors positive for the proliferation markers ki67 and EdU as well as the cone-specific retinoic acid receptor RXRy. From E18 onwards the EGFP-positive cells were observed at the apical side of the retina where the post mitotic RxRy-positive cone photoreceptors are confined. The ability of different cell populations collected from embryonic and postnatal retinas to integrate and replace dying cones was assessed by transplantation in retinas of different mouse models of cone-rod dystrophy or retinitis pigmentosa such as CNGA3-/- and rd10 respectively as well as in NOD-SCID immunodeficient mice. The grafting efficiency is highly influenced by the donor age, subpopulation of selected cells as well as disease type and progression, underlying the need to collect cones at a specific ontogenetic stage and to treat retinas before a critical degeneration time point. After transplantation many cells accumulate in the subretinal space of recipient retinas and express immature progenitor markers or proteins of the phototransduction pathway depending on the age of donor cells and on the type of disease treated. Few cones morphologically integrated the degenerated retina displaying a mature morphology. Nonetheless, the number of incorporated transplanted cones exceeded the number of cone integration of previous published studies.
In conclusion, the Chrnb4-EGFP mouse line analyzed in this work provides a tool to investigate the potential of cones to integrate adult degenerating retinas after transplantation. More efforts are still needed to reveal factors limiting cone integration and maturation in adult grafted retinas.
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