June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
PRPH2-associated alterations in retinal function and morphology involve inflammatory responses in a CRISPR-generated mouse model
Author Affiliations & Notes
  • Oksana Kutsyr Kolesnyk
    Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain
  • María José Ruiz-Pastor
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Xavier Sánchez-Sáez
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Carla Sánchez-Castillo
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Henar Albertos-Arranz
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Natalia Martínez-Gil
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Isabel Ortuño-Lizarán
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Lorena Vidal-Gil
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Laura Fernández-Sánchez
    Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain
  • Agustina Noailles
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Victoria Maneu
    Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain
  • Pedro Lax
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Nicolas Cuenca
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Footnotes
    Commercial Relationships   Oksana Kutsyr Kolesnyk None; María José Ruiz-Pastor None; Xavier Sánchez-Sáez None; Carla Sánchez-Castillo None; Henar Albertos-Arranz None; Natalia Martínez-Gil None; Isabel Ortuño-Lizarán None; Lorena Vidal-Gil None; Laura Fernández-Sánchez None; Agustina Noailles None; Victoria Maneu None; Pedro Lax None; Nicolas Cuenca None
  • Footnotes
    Support  Spanish Ministry of Science and Innovation (FEDER-PID2019-106230RB-I00), Spanish Ministry of Universities (FPU18/02964), National Institute of Health Carlos III (RETICS-FEDER-RD16/0008/0016), Generalitat Valenciana (IDIFEDER/2017/064, PROMETEO/2021/024, ACIF/2020/203) and University of Alicante (MARSALAS21-35).
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1548. doi:
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      Oksana Kutsyr Kolesnyk, María José Ruiz-Pastor, Xavier Sánchez-Sáez, Carla Sánchez-Castillo, Henar Albertos-Arranz, Natalia Martínez-Gil, Isabel Ortuño-Lizarán, Lorena Vidal-Gil, Laura Fernández-Sánchez, Agustina Noailles, Victoria Maneu, Pedro Lax, Nicolas Cuenca; PRPH2-associated alterations in retinal function and morphology involve inflammatory responses in a CRISPR-generated mouse model. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1548.

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

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Abstract

Purpose : A broad range of inherited retinal diseases, including central areolar choroidal dystrophy (CACD), is associated with mutations in the PRPH2 gene. Here we aimed to characterize a mouse model with p.Arg195Leu mutation in the PRPH2 gene, previously described in human patients.

Methods : Appling the CRISPR/Cas9 system to insert the Arg195Leu mutation, we generated Prph2WT/KI and Prph2KI/KImice models. To characterize both models at different time points, we analyzed retinal function by electroretinography and optomotor test. The structural integrity and the morphology of the retina were studied using optical coherence tomography (OCT), immunohistochemistry, and TEM images. Additionally, we used flow cytometry to evaluate the inflammatory state of the retina.

Results : A progressive retinal degeneration was found affecting both Prph2WT/KI and Prph2KI/KI mice models. Significantly decreased retinal function from 3 months of age in Prph2KI/KI and 6 months of age in Prph2WT/KIwas correlated with progressive degeneration of the outer nuclear layer shown by OCT images. Using specific markers, we found unstructured and shortened photoreceptor outer segments. Moreover, TEM images confirmed an abnormal stacking and alignment of photoreceptor discs. Furthermore, retinal degeneration found in both mice models was associated with an increased inflammatory state of the retina. Flow cytometry analyses showed an increased CD11b+CD11chiMHCII+ population over time.

Conclusions : Prph2WT/KI and Prph2KI/KI mice models showed progressive retinal degeneration and aberrant formation of photoreceptor outer segments, displaying a similar pattern to that found in patients with the same retinal dystrophy. Thus, this mice model can be suitable for further CACD characterization and evaluation of different therapeutic strategies.

Support: Spanish Ministry of Science and Innovation (FEDER-PID2019-106230RB-I00), Spanish Ministry of Universities (FPU18/02964), National Institute of Health Carlos III (RETICS-FEDER-RD16/0008/0016), Generalitat Valenciana (IDIFEDER/2017/064, PROMETEO/2021/024, ACIF/2020/203) and University of Alicante (MARSALAS21-35).

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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