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Restoration of night vision in adult mice

Complete congenital night blindness (CCNCS) is an incurable hereditary disease and a group of rare, clinically and genetically heterogeneous retinal disorders.

Patients with this condition suffer from poor visual acuity, difficulty in orienting themselves in low light (scotopic) conditions and often have high myopia. These patients are not able to move around in a cinema or in a street lit by a street lamp, which is socially very disabling. It is difficult to estimate the number of patients affected by CCNCS because its diagnosis requires special ophthalmological examinations. Indeed, CCNCS is characterised by a decrease in the visual response measured on the electroretinogram, which reflects a defect in the transmission of visual information between the photoreceptors and the bipolar cells of the retina. As the disease is non-degenerative and stable, the treatment could theoretically be administered at any time in life, making it a promising target for gene therapy.

In order to test the effectiveness of gene therapy, two mouse models mutated on the Grm6 and Lrit3 genes, which mimic the clinical signs found in patients affected by CCNCS in low light conditions, were generated. In 2021, work carried out at the Institut de la Vision, which targeted photoreceptors and/or bipolar cells in these two mouse models by gene therapy, revealed a restoration of the localisation of the deficient proteins and their partners (see image), as well as an improvement in the transmission of the visual signal confirmed by electroretinograms, multi-electrode array recordings as well as by behavioural responses carried out in the optometer. These very promising approaches can be tested on larger animals, whose morphology and physiology are closer to those of the human eye, before moving on to clinical trials for a potential treatment for CCNCS.

This work was made possible thanks to the support of patient associations such as Retina France, AFM, UNADEV and the FRM. Juliette Varin, together with other scientists from the Institut de la Vision, under the direction of Dr Christina Zeitz, have published these results in the excellent journals Investigative Ophthalmology & Visual Science (IOVS) and Molecular Therapy - Methods and Clinical Development.

Original Publication

Restoration of mGluR6 Localization Following AAV-Mediated Delivery in a Mouse Model of Congenital Stationary Night Blindness
Juliette Varin  1 Nassima Bouzidi  1 Miguel Miranda De Sousa Dias  1 Thomas Pugliese  1 Christelle Michiels  1 Camille Robert  1 Melissa Desrosiers  1 José-Alain Sahel  1   2   3   4   5 Isabelle Audo  1   2   6 Deniz Dalkara  1 Christina Zeitz  1 . 2021 Mar 1;62(3):24. doi: 10.1167/iovs.62.3.24.