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November 8, 2010

Blind Dogs That Can See: Pharmacological Treatment of Leber Congenital Amaurosis Caused by a Defective Visual Cycle

Author Affiliations

Author Affiliation: Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio.

Arch Ophthalmol. 2010;128(11):1483-1485. doi:10.1001/archophthalmol.2010.245

Petersen-Jones and colleagues performed an important proof-of-principle study titled “Improvement of Visual Performance With Intravitreal Administration of 9-cis-Retinal in Rpe65-Mutant Dogs,”1 published in this issue of the Archives. As a component of comprehensive preclinical studies, its primary goal was to determine the efficacy of 9-cis-retinal in restoring visual function assessed by both electroretinography (ERG) and functional vision testing in Rpe65-mutant dogs. Because dogs generally have high levels of circulating retinoids,2 the researchers injected 9-cis-retinal directly into 1 eye of 7 Briard Rpe65−/−-mutant dogs (Figure, A).3,4 The results were striking. In 5 of 7 dogs, 9-cis-retinal injection resulted in increased rod ERG responses and improved functional vision. Moreover, 3 injected dogs exhibited increased 33-Hz flicker amplitudes characteristic of cone-mediated responses. These positive effects lasted for about 10 weeks. More important, a second injection of 9-cis-retinal at 20 or 29 weeks after the first injection in 2 (dogs 5 and 6) of the 7 dogs partially restored vision again, providing a potential dosing strategy for humans. These encouraging results provide impetus for the development of intravitreal devices that promote sustained delivery of 9-cis-retinal as a therapy for conditions resulting from a genetic blockade of the retinoid (visual) cycle (Figure, B).

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