Function and Structure in Retinal Transplants

Embryonic mammalian donor retina transplanted into the subretinal space of a mature host develops into a graft with wellorganized, but atypical retinal structure. We tested the effect of this organization on rabbitto-rabbit graft functional properties, isolating the graft to avoid contamination of graft responses by host retinal activity. Transient ON or ON-OFF spike-like responses and local electroretinograms (L-ERGs) were recorded simultaneously via a single electrode on the graft surface. These response components depended on stimulus diameter, sometimes in a way indicating antagonistic center-surround receptive field organization and spatial tuning (43%). Other times, the responses were an increasing function of stimulus diameter which saturated for large spots (57%). Response amplitudes were transplantation surgery is to be done with therapeutic aims

Ultrastructural Circuitry in Retinal Cell Transplants to Rat Retina

The development of five transplants of fetal retinal tissue to adult rat eyes was examined with the electron microscope. The transplants were of 9 to 10 weeks total age after conception in four cases and 20 weeks in one case. They were at stage E15 when transplanted. Transplants developed in both the epiretinal and subretinal spaces

Effects of ethanol on photoreceptors and visual function in developing zebrafish

PURPOSE. Children born to mothers who have consumed alcohol during pregnancy have an array of retinal abnormalities and visual dysfunctions. In the past, rodent systems have been used to study the teratogenic effects of ethanol on vertebrate embryonic development. The exact developmental windows in which ethanol causes specific developmental defects have been difficult to determine because rodents and other mammals develop in utero. In this study, we characterized how ethanol affects the function and development of the visual system in an ex utero embryonic system, the zebrafish. METHODS. Zebrafish embryos were raised in fish water containing various concentrations of ethanol from 2 to 5 days after fertilization. The effects of ethanol on retinal morphology were assessed by histologic and immunohistochemical analyses and those on retinal function were analyzed by optokinetic response (OKR) and electroretinography (ERG). RESULTS. Zebrafish embryos exposed to moderate and high levels of ethanol during early embryonic development had morphological abnormalities of the eye characterized by hypoplasia of the optic nerve and inhibition of photoreceptor outer segment growth. Ethanol treatment also caused an increased visual threshold as measured by the OKR. Analysis with the ERG indicated that there was a severe reduction of both the a-and b-waves, suggesting that ethanol affects the function of the photoreceptors. Indeed, low levels of ethanol that did not cause obvious morphologic changes in either the body or retina did affect both the OKR visual threshold and the a-and b-wave amplitudes. CONCLUSIONS. Ethanol affects photoreceptor function at low concentrations that do not disturb retinal morphology. Higher levels of ethanol inhibit photoreceptor development and cause hypoplasia of the optic nerve. (Invest Ophthalmol Vis Sci. 2006;47:4589 -4597) DOI:10.1167/iovs.05-0971 S ome children born to mothers who have consumed alcohol during pregnancy have a number of morphologic, sensory, and cognitive abnormalities, including vision deficits, collectively known as fetal alcohol syndrome (FAS). It was originally thought that FAS was the result of alcohol abuse; however, smaller doses or shorter durations of prenatal alcohol consumption also produce harmful, though more subtle, effects referred to as alcohol-related birth defects (ARBDs) or alcoholrelated neurodevelopment disorder (ARND). 1 Even though FAS was described several decades ago, 2 little is known about the mechanistic underpinnings of ethanol teratogenicity. 3 The retina is one of the organs affected by ethanol during embryogenesis. As many as 90% of children in whom FAS is diagnosed have some type of ocular problem, ranging from microphthalmia and retinal dysmorphologies to reduced visual function. One of the challenges of analyzing ethanol's teratogenicity in vertebrates using rodents as model systems is that mammals develop in utero. Therefore, ethanol concentrations and exposure times that result in a specific phenotype are difficult to determine because the metabolic function of the mother must be considered. Other vertebrates, such as zebrafish and Xenopus laevis, develop ex utero, so specific concentrations of ethanol over specific developmental periods are easily achieved. Treating zebrafish and Xenopus embryos with ethanol results in phenotypes comparable to those described for children with FAS, suggesting that the same molecular mechanisms are disturbed by ethanol treatment in vertebrates. 9 -11 Moreover, unlike mouse, zebrafish contain abundant cone photoreceptors that differentiate relatively early, making it a better system for the study of color vision in vertebrates. MATERIALS AND METHODS Breeding Fish and Treating Zebrafish Embryos with Ethanol Ekkwill and AB strain zebrafish were maintained as an inbred stock at the Harvard zebrafish facility and were bred as previously described