Howard C. Howland - US grants

These researches are directed at finding a practical method for identifying infants and young children who are at risk of developing amblyopia due either to uncorrected refractive errors or subtle motor problems. They are also aimed at finding the physiological basis of an effective preventative therapy for refractive amblyopia and severe ametropia by investigating emmetropizing mechanisms in humans and animals. To accomplish these goals it is proposed to conduct both human and animal studies on refractive development. In the human work, our 15 year longitudinal study of refractive development will be extended by refracting infants and children of our volunteer population with visible light photorefractive and infrared autorefractive methods. In particular a new binocular infrared autorefractive method, developed partially in our laboratory, will be employed. Data on parental and familial refractive status will also be gathered. This refractive data will be used to construct a practical method for the prediction and, hopefully, the prevention of amblyopia on the basis of refractive and motor behavior measured in infancy. The laboratory's animal work will continue to concentrate on the study of the growth of eyes of chicks, focusing now on the image-directed regulation of growth of the anterior chamber. We will investigate the nature of the compensation for astigmatic defocus, and we will employ conditions of constant light to isolate one of the two important feedback mechanisms of image controlled growth. We will also examine the optical methods by which the chick eye maintains optical quality during accommodation in the face of a large change of aberration structure of the cornea. From a knowledge of the emmetropization mechanisms of chicks, we hope to gain insights into both the normal and the pathological development of human refractive states.

DESCRIPTION (Adapted from Applicant's Abstract): This grant addresses aspects of the general question: how do neural and hormonal pathways work together to establish regulation of refraction and growth of both eyes during early postnatal development? These pathways are important in coordinating development of eye movements, eye size, refraction and emmetropization. As such, their investigation is of singular importance in understanding the genesis of refractive error, strabismus, and amblyopia in humans. This study is particularly focused on the regulation of growth of the anterior segment of the eye. Using the chick model we will 1a) determine if the signal responsible for protection from constant light effects (flattened cornea, shallow anterior chamber & hyperopia) is a periodic increase in melatonin concentration, and investigate the causal chain linking illumination and melatonin concentrations; 1b) determine whether the elongation of the vitreous chamber in constant light results from emmetropization growth, induced by the hyperopia that is caused by the flattening of the cornea; 1c) investigate the role of autonomic effects on the growth of the anterior segment; 2) investigate the light-dependent growth influences of one eye on another by various manipulations including optic nerve section, selective retinal cell destruction by drugs, and the generation of unilaterally micro-ophthalmic chicks. 3) investigate the mode of coupling of the light dark cycle to the circadian melatonin rhythm with the aid of mathematical models. Behavioral, surgical, biochemical, histological, and mathematical methods will be employed to answer these questions.