Retinopathy, globe enlarged

The purpose of this study was to perform a detailed characterization of the clinical, electroretinographic and morphological aspects and a preliminary molecular characterization of the autosomal recessive retinopathy, globe enlarged (rge) phenotype in chickens. Rge affected, carrier and normal birds were examined in detail ophthalmoscopically. A morphometric assessment of the eye globe and vision testing with an optokinetic device were performed. Scotopic and photopic electroretinography (ERG) and visually evoked potentials (VEPs) were recorded. Pharmacological investigation of abnormal ERG responses of rge birds was carried out. Morphological features were examined by light and electron microscopy. Retinal cell counting and measurement of the thickness of retinal layers were performed. Immunohistochemical staining with a panel of several antibodies was also investigated. Rge chicks lose vision over the first few weeks of life and are functionally blind by 30 days of age. They develop thicker corneas with a larger radius of curvature, hyperopia, and enlarged globes both radially and axially. At 1 day of age they have an elevated photopic and scotopic ERG response threshold, lower ampli/tude for a-wave and a substantial decrease of both oscillatory responses (OPs) and c-waves. With bright flash intensities, a supernormal b-wave response is present during the first weeks of life. All ERG responses decrease with increasing age. Naka-Rushton analysis of the ERG shows it is clearly abnormal from 1 day of age. After the rge chicks are functionally blind, optokinetic and cortical responses suggest some degree of vision (judged by the optokinetic performance) remains, although very reduced. Failure to block the b-wave responses with intravitreal injections of glutamate analogues (PDA and APB) provides strong evidence that the cells that normally generate this response in normal chicks do not originate the b-wave of rge chicks. Intravitreal injections of BaCl2 enhanced the supernormal b-wave response and ornithine nearly abolished it. Early morphological changes observed in rge retinas were disorganization of the outer plexiform layer and abnormal location of the smooth endoplasmic reticulum of the photoreceptors. A microsatellite marker (MCW0318) co-segregated with the rge locus, indicating that human chromosome region 12 p11--13 is the most likely region to contain the human homolog of the rge gene. Future identification of the causal gene mutation should help explain the morphological and ERG abnormalities of the rge phenotype and account for the rapid development of vision deficits.