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).
Treatment of Briard Rpe65−/−-mutant dogs with the synthetic cis-retinoids. A, View of a treated Briard Rpe65−/−-mutant dog. B, Chemistry of vision: phototransduction and the retinoid (visual) cycle (reviewed in von Lintig et al3). Mutations in Rpe65 are associated with Leber congenital amaurosis4 because they are required for 11-cis-retinal production. 9-cis-Retinoids can be used to overcome this blockage and regenerate functional visual pigments, called isorhodopsin, in rods that have characteristics similar to rhodopsin. The depicted protein structures are of rhodopsin (left) and Rpe65 (right).
Thank you for submitting a comment on this article. It will be reviewed by JAMA Ophthalmology editors. You will be notified when your comment has been published. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest*
Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 5
Customize your page view by dragging & repositioning the boxes below.
More Listings atJAMACareerCenter.com >
Users' Guides to the Medical Literature
Solving the Problem: What are Confidence Intervals?
Users' Guides to the Medical Literature
A Real-World Example of a Randomized Trial of Drug Therapy
All results at
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.