Dark adaptation of rod photoreceptors in normal subjects, and in patients with Stargardt disease and an ABCA4 mutation.

Abstract

PURPOSE:

Psychophysical and electroretinographic (ERG) studies indicate that patients with Stargardt disease exhibit abnormally slow rod dark adaptation after illumination that bleaches a substantial fraction of rhodopsin. However, relatively little information is available concerning rod recovery in this disease after weaker adapting (i.e., conditioning) light. With the use of a paired-flash ERG method, properties of the derived rod response to a low-bleach (<1%) but rod-saturating conditioning flash were investigated in seven normal subjects and in five Stargardt patients with identified sequence variations in the ABCA4 gene.

METHODS:

In the first of two experiments, the interval between a fixed conditioning flash (67 or 670 scotopic cd s m(-2)) and a bright probe flash of fixed strength was varied to determine the falling-phase kinetics of the derived rod response to the conditioning flash. In the second, the instantaneous amplitude-intensity function for the rod response at an intermediate stage of recovery from the conditioning flash was determined by presenting a test flash of various strengths at a fixed time after the conditioning flash, and a probe flash at 200 ms after the test flash.

RESULTS:

The maximum peak amplitude of the dark-adapted, rod-mediated a-wave determined in Stargardt patients (211 +/- 87 microV) was on average lower than that determined in normal subjects (325 +/- 91 microV; P = 0.06). The derived rod response to the 670 scotopic cd s m(-2) conditioning flash determined in normal subjects and Stargardt patients exhibited a biphasic recovery, and the kinetics of the early stage of this recovery were similar in the two subject groups. For both normal subjects and patients, normalized amplitude-intensity functions describing the dark-adapted derived rod response exhibited half-saturation at approximately 1.5 log scotopic troland second. In both groups, the normalized amplitude-intensity function determined at approximately 2 seconds after the 67 scotopic cd s m(-2) conditioning flash and at approximately 9 seconds after the 670 scotopic cd s m(-2) conditioning flash exhibited an average desensitization (i.e., an increase of test flash strength at half-saturation) of approximately 0.5 to 0.6 log unit relative to that determined under dark-adapted conditions.

CONCLUSIONS:

The results indicate that, despite a reduction in the average dark-adapted maximum a-wave amplitude in the Stargardt/ABCA4 patients, the early-stage recovery kinetics of the derived rod response to a low-bleaching conditioning flash as well as the lingering rod desensitization produced by such a flash are similar to those determined in normal subjects.

• Authors: Jennifer J Kang Derwent, Deborah J Derlacki, John R Hetling, Gerald A Fishman, David G Birch, Sandeep Grover, Edwin M Stone, David R Pepperberg
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 45 Issue 7 Pg. 2447-56 (Jul 2004) ISSN: 0146-0404 [Print] United States
• PMID: 15223829 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• ABCA4 protein, human
• ATP-Binding Cassette Transporters
• Vitamin A
• Rhodopsin

Topics

• ATP-Binding Cassette Transporters (genetics)
• Adult
• Dark Adaptation (physiology)
• Electroretinography
• Female
• Humans
• Male
• Middle Aged
• Mutation (physiology)
• Photic Stimulation
• Retinal Diseases (genetics, physiopathology)
• Retinal Rod Photoreceptor Cells (physiology)
• Rhodopsin (metabolism)
• Vitamin A (metabolism)