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

Arch Ophthalmol. 2010 Nov;128(11):1442-8. doi: 10.1001/archophthalmol.2010.210. Epub 2010 Sep 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics*
  • Dark Adaptation
  • Disease Models, Animal*
  • Diterpenes
  • Dogs
  • Electroretinography
  • Eye Proteins / genetics*
  • Female
  • Intravitreal Injections
  • Isomerism
  • Leber Congenital Amaurosis / drug therapy*
  • Leber Congenital Amaurosis / genetics
  • Leber Congenital Amaurosis / physiopathology
  • Male
  • Mutation*
  • Photoreceptor Cells, Vertebrate / physiology*
  • Retinaldehyde / administration & dosage*
  • Retreatment
  • Vision, Ocular / physiology*
  • Visual Acuity / physiology


  • Carrier Proteins
  • Diterpenes
  • Eye Proteins
  • 9-cis-retinal
  • Retinaldehyde