OBJECTIVE: To determine the efficacy of intravitreal administration of 9-cis-retinal in restoring visual function in Rpe65-mutant dogs. METHODS: Intravitreal injection of 9-cis-retinal was administered in 1 eye of 7 Rpe65-/- dogs at a range of ages. Electroretinogram analysis and testing of visual performance was used to evaluate outcomes after a single injection and in 2 dogs after a second injection in the same eye. RESULTS: In 5 of 7 injected dogs, 9-cis-retinal injection resulted in increased rod electroretinogram responses and improved functional vision. Three injected dogs exhibited increased 33-Hz flicker amplitudes characteristic of cone-mediated responses. Electroretinogram improvement was no longer evident by week 10 postinjection in 1 dog monitored over time. A second injection of 9-cis-retinal was performed in the same eye of 2 of the 7 dogs and also resulted in rescue of visual function. CONCLUSION: Our findings establish that 9-cis-retinoid therapy can restore visual function in a canine model of human disease resulting from RPE65 mutations. CLINICAL RELEVANCE: These positive proof-of-principle results provide support for the development of intravitreal devices for sustained delivery of 9-cis-retinal as a therapy for conditions resulting from failure of the visual cycle.
OBJECTIVE: To determine the efficacy of intravitreal administration of 9-cis-retinal in restoring visual function in Rpe65-mutant dogs. METHODS: Intravitreal injection of 9-cis-retinal was administered in 1 eye of 7 Rpe65-/- dogs at a range of ages. Electroretinogram analysis and testing of visual performance was used to evaluate outcomes after a single injection and in 2 dogs after a second injection in the same eye. RESULTS: In 5 of 7 injected dogs, 9-cis-retinal injection resulted in increased rod electroretinogram responses and improved functional vision. Three injected dogs exhibited increased 33-Hz flicker amplitudes characteristic of cone-mediated responses. Electroretinogram improvement was no longer evident by week 10 postinjection in 1 dog monitored over time. A second injection of 9-cis-retinal was performed in the same eye of 2 of the 7 dogs and also resulted in rescue of visual function. CONCLUSION: Our findings establish that 9-cis-retinoid therapy can restore visual function in a canine model of human disease resulting from RPE65 mutations. CLINICAL RELEVANCE: These positive proof-of-principle results provide support for the development of intravitreal devices for sustained delivery of 9-cis-retinal as a therapy for conditions resulting from failure of the visual cycle.
Authors: R F Boyd; S L Boye; T J Conlon; K E Erger; D G Sledge; I M Langohr; W W Hauswirth; A M Komáromy; S E Boye; S M Petersen-Jones; J T Bartoe Journal: Gene Ther Date: 2016-04-07 Impact factor: 5.250
Authors: R F Boyd; D G Sledge; S L Boye; S E Boye; W W Hauswirth; A M Komáromy; S M Petersen-Jones; J T Bartoe Journal: Gene Ther Date: 2015-10-15 Impact factor: 5.250
Authors: Shirin Kahremany; Christopher Lane Sander; Gregory P Tochtrop; Adam Kubas; Krzysztof Palczewski Journal: Org Biomol Chem Date: 2019-08-28 Impact factor: 3.876
Authors: Rebecca Ward; Joanna J Kaylor; Diego F Cobice; Dionissia A Pepe; Eoghan M McGarrigle; Susan E Brockerhoff; James B Hurley; Gabriel H Travis; Breandán N Kennedy Journal: J Biol Chem Date: 2020-04-01 Impact factor: 5.157