Doctors - Research Highlights

Highlights of Major Accomplishments - The Fulton Group

* Demonstration of a rapid increase in ocular rhodopsin content during early infancy,

* Discovery that during development rod photoreceptor sensitivity determines dark-adapted, rod-mediated visual sensitivity,

* Demonstration of impaired dark-adapted thresholds in infants with a history of mild retinopathy of prematurity considered to have resolved completely at the time of study.

Major Results - The Fulton Group

1. Normal development of rhodopsin content
Rod phototransduction begins with photon capture by rhodopsin. We reasoned that, in development, rod photoreceptor sensitivity is low because the amount of rhodopsin is low. The total amount of rhodopsin in human eyes was measured to test the hypothesis that the rhodopsin content of infants' eyes is lower than the content at later ages. Rhodopsin was extracted from 196 eyes of 102 donors, ages 27 weeks‰ gestation through 94 years, using quantitative procedures. Controls for bleaching were used. Rhodopsin content per eye was examined for significant change with age. The median rhodopsin content in adults is 6.45 nmoles (range, 3.33-10.84 nmoles) with 8 nmoles or more recovered from 28% of all adult eyes. The rhodopsin content of infants‰ eyes (<12 months post-term) is significantly lower than the content of older individuals and increases with age. After infancy, no change with age is found. The rhodopsin content early in infancy, i.e., approximately 5 weeks post term, is approximately 50% of the median adult amount. We conclude that a developmental increase in rhodopsin content occurs during infancy and that rhodopsin content thereafter remains constant.

2. Development of rod photoreceptor and scotopic visual sensitivity
We next addressed the question: what determines infants‰ low scotopic visual sensitivity, the immature rods or post receptoral processing? This issue has long been debated. We used ERG and psychophysical procedures to study the course of development of rod photoreceptor sensitivity and dark-adapted visual sensitivity. The shape of the logistic growth curve and the age at which sensitivity reaches 50% of the adult value are similar (10 to 13 weeks) for the rods and peripheral visual sensitivity. A parsimonious explanation is that during development rod photoreceptor sensitivity determines dark adapted, rod mediated visual sensitivity. The maturation of the parafoveal visual sensitivity is delayed, as is the development of parafoveal rod outer segments, compared to the sensitivity at more peripheral retinal sites.

3. Other ERG studies of photoreceptor function
We have completed ERG studies of the deactivation of rod phototransduction in normal 10-week-old infants and adult controls. The recovery times of 10-week-old infants (median 6.6; range 4.3-13.9sec) are, on average, more than twice as long as those of adults (median 2.7, 1.9-4.6sec). The results of a study of activation of cone phototransduction in 10 four-week-old and 20 ten-week old infants as well as in adult controls show that the cone photoresponses of the infants are much more like those of adults than are the rod photoresponses. The relative maturity of the cone photoresponse is consistent with the early anatomical development of the cones.

4. Psychophysical studies of scotopic vision
We have completed several investigations of rod photoreceptor function represented by scotopic visual thresholds in normal infants, and we have begun studies in ROP subjects. The developmental course of dark adapted thresholds in normal, term infants' parafoveal (10o eccentric) and peripheral (30o eccentric) retinas were measured using a within-subject longitudinal design, starting at age 10 weeks. In adults, the thresholds at these sites are equal. The results from normal infants are in sharp contrast to the preliminary results from infants with a history of mild ROP that had resolved completely by the time that these measures of their vision were performed. We suspect that the slower maturing rods in the parafoveal retina are more susceptible to the processes that cause ROP. These preliminary results provide the background for new experiments in infants and children with ROP. The main hypothesis to be tested is that the more severe the acute phase ROP, the more severe the photoreceptor dysfunction.