Disruption of the centrifugal visual system inhibits early eye growth in chicks

Emmetropization, the process by which neonatal refractive errors are reduced toward zero, is partially dependent on brain-retina connectivity. Here, we investigated the role of the centrifugal visual system, a visually driven retinal feedback projection, as one potential influence on this complex mechanism. Lesions of the isthmo-optic nucleus/tract or sham surgeries were performed in fifty-four 4- to 5-day-old chicks to disrupt centrifugal efferents to the contralateral retina. Prior to surgery, baseline refractive error measurements were made using streak retinoscopy. Postoperative ocular phenotyping, which (in addition to retinoscopy) comprised A-scan ultrasonography and infrared keratometry, was performed 7 days and 21 days postsurgery. A pathway-tracing paradigm was used to determine lesion success, whereby an injection of wheat-germ agglutinin was made into the vitreous chamber contralateral to the lesion. Postmortem, tissue processing, immunohistochemistry, and stereological analysis of intact centrifugal neurons were performed. Subsequently, chicks were divided into quartile groups based on percentage lesion success. Seven days postsurgery, chicks in the quartile of highest percentage lesion success exhibited significant axial hyperopia in the "treated eye" (contralateral to the lesion) relative to the "control eye" (ipsilateral to the lesion) eye, when compared with subjects within quartile groups of lower percentage lesion success (P = 0.004). However, by 21 days postsurgery, the induced hyperopia was no longer evident. Unilateral disruption of centrifugal efferents to the retina of the contralateral eye induces an initial axial hyperopia, which is subsequently reversed through increased vitreous elongation in the affected eyes.