Improvement of visual performance with intravitreal administration of 9-cis-retinal in Rpe65-mutant dogs.
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.


CONCLUSIONS
Our findings establish that 9-cis-retinoid therapy can restore visual function in a canine model of human disease resulting from RPE65 mutations.


CONCLUSIONS
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.
Gearhart
Patricia M
PM
Department of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI 48824, USA.
Gearhart
Chris
C
Thompson
Debra A
DA
Petersen-Jones
Simon M
SM
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D003623:Dark Adaptation; D004195:Disease Models, Animal; D004224:Diterpenes; D004285:Dogs; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D058449:Intravitreal Injections; D007536:Isomerism; D057130:Leber Congenital Amaurosis / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D009154:Mutation; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D012172:Retinaldehyde / Q000008:administration & dosage*; D019233:Retreatment; D014785:Vision, Ocular / Q000502:physiology*; D014792:Visual Acuity / Q000502:physiology
D002352:Carrier Proteins; D004224:Diterpenes; D005136:Eye Proteins; C031390:9-cis-retinal; D012172:Retinaldehyde