June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Dendritic cells are recruited to the outer retina by cone death in a mouse model for Type 2 Leber congenital amaurosis
Author Affiliations & Notes
  • Peter Hao Tang
    Ophthalmology & Visual Neurosciences, University of Minnesota, Minneapolis, MN
  • Mark J Pierson
    Ophthalmology & Visual Neurosciences, University of Minnesota, Minneapolis, MN
  • Neal D Heuss
    Ophthalmology & Visual Neurosciences, University of Minnesota, Minneapolis, MN
  • Dale S Gregerson
    Ophthalmology & Visual Neurosciences, University of Minnesota, Minneapolis, MN
  • Footnotes
    Commercial Relationships Peter Tang, None; Mark Pierson, None; Neal Heuss, None; Dale Gregerson, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2080. doi:https://doi.org/
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      Peter Hao Tang, Mark J Pierson, Neal D Heuss, Dale S Gregerson; Dendritic cells are recruited to the outer retina by cone death in a mouse model for Type 2 Leber congenital amaurosis. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2080. doi: https://doi.org/.

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

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Abstract

Purpose: Using the CD11c-DTR/GFP mice, we have previously shown that GFP+ dendritic cells (DC) were recruited to retina following optic nerve crush injury (ONC). Cells were heavily concentrated in the retinal ganglion cell/nerve fiber layer (RGC/NFL), consistent with the site of injury, and in the outer plexiform layer. Other studies showed they were the antigen-presenting cells (APC) within the retina. To explore if GFP+ DC home to the site of injury, mice exhibiting photoreceptor degeneration were tested. Mutation of the gene encoding RPE65 protein leads to disruption of innate retinoid metabolism and development of Type 2 Leber congenital amaurosis (LCA2), a form of retinal dystrophy characterized by early-onset of cone death and progressive visual impairment. Details of the mechanism for cone death in this disease remain unknown. We investigated the timing, localization and role of DC associated with cone death in a mouse model for LCA2.

Methods: To develop the animal model, Rpe65-/- mice were bred to transgenic mice whose DC expressed a chimeric protein containing GFP and diphtheria toxin receptor driven by a CD11c promoter (CD11c-DTR/GFP mice). Progeny were screened by PCR and immunoblotting to confirm transgenic Rpe65-/- mice along with Rpe65+/+ and Rpe65+/- mice as controls. Cone survival was evaluated by counts from retinal flatmounts stained for cone opsins, and morphology was further evaluated by cryosections of transgenic Rpe65-/- and Rpe65+/+ mice.

Results: Homozygous knockout of the Rpe65 gene from progeny that was bred to the transgenic CD11c-DTR/GFP background was confirmed through PCR and immunoblotting. In these mice, cone counts showed massive cone death compared to Rpe65+/+ transgenic mice. Morphology showed increased GFP+ cells within the outer retina in Rpe65-/- mice compared to controls. The DC were concentrated within the areas of cone death, unlike their homing to the RGC/NFL following an ONC.

Conclusions: These results show that the GFP+ DC were recruited to the site of injury or stress. In contrast to the results with an ONC to the RGC, the GFP+ DC in the RPE65-/- mice were recruited to outer retina by the death of cone cells due to disruption of intrinsic retinoid metabolism as seen in LCA2. The presence and activity of these cells may have implications for novel therapeutics involving immune cells in the treatment for congenital retinal dystrophies.

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