Histogenesis of the ferret retina

Greineer, Jack V.; Weidman, Thomas A.

doi:10.1016/s0014-4835(81)80055-3

Cited by 81 publications

(56 citation statements)

References 8 publications

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“…A fainter, but clear staining was present around the cell body of the cone photoreceptors. The cell bodies of cones are located at the border between the outer nuclear layer and the inner segment area 21 confirming the specificity of our staining. Although most of the GFP-positive photoreceptors were rods, in a minority of cells GFP colocalized precisely with peanut agglutinin staining of cones.…”

Section: Raav-mediated Transduction Of Cone Photoreceptorssupporting

confidence: 83%

Stable rAAV-mediated transduction of rod and cone photoreceptors in the canine retina

et al. 2003

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Recombinant adeno-associated virus (rAAV) vectors are attractive candidates for the treatment of inherited and acquired retinal disease. Although rAAV vectors are well characterized in rodent models, a prerequisite to their clinical application in human patients is the thorough evaluation of their efficacy and safety in intermediate animal models. In this study, we describe rAAV-2-mediated expression of GFP reporter gene in retinal cells following local vector delivery in dogs. Subretinal delivery of rAAV.CMV.GFP was performed unilaterally in eight normal dogs from 6 weeks of age. The area of retinal transduction was maximized by the optimization of surgical techniques for subretinal vector delivery by pars-plana vitrectomy and the use of fine-gauge subretinal cannulae to create multiple retinotomies. rAAV-2 vectors mediated efficient stable reporter gene expression in photoreceptors and retinal pigment epithelial cells. We found efficient transduction of cone photoreceptors in addition to rods in both the canine retina and after subretinal vector delivery in another intermediate animal model, the feline retina. GFP expression in dogs was confined to the area of the retinal bleb and was sustained in cells at this site for at least 18 months. Electroretinography demonstrated a modest reduction in global rod-mediated retinal function following subretinal delivery of rAAV.CMV.GFP. Three of the eight animals developed delayed-onset intraocular inflammation, in two cases associated with a serum antibody response to GFP protein. We conclude that rAAV-2 vectors mediate efficient sustained transgene expression in rod and cone photoreceptors following subretinal delivery in this intermediate animal model. The possibility of adverse effects including intraocular immune responses and reduced retinal function requires further investigation prior to clinical applications in patients.

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Section: Raav-mediated Transduction Of Cone Photoreceptorssupporting

confidence: 83%

Stable rAAV-mediated transduction of rod and cone photoreceptors in the canine retina

et al. 2003

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“…Interestingly, this demonstrates that rather different mechanisms can be used to regulate sequential aspects of development in the same pathway. NMDA receptors and NO are well suited to mediate the later sharpening of connections into ON/OFF sublaminae, which is accompanied by the maturation of photoreceptors and bipolar cells in the ferret retina and their functional connections to retinal ganglion cells (Greiner and Weidman, 1981) (cf. Maslim and Stone, 1986).…”

Section: Discussionmentioning

confidence: 99%

A Role for Nitric Oxide in the Development of the Ferret Retinogeniculate Projection

et al. 1996

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The ferret retinogeniculate projection segregates into eyespecific layers during the first postnatal week and into ON/OFF sublaminae, which receive inputs from either on-center or offcenter retinal ganglion cells, during the third and fourth postnatal weeks. The restriction of retinogeniculate axon arbors into eye-specific layers appears to depend on action potential activity (Shatz and Stryker, 1988) but does not require activation of NMDA receptors (Smetters et al., 1994). The formation of ON/OFF sublaminae is also activity-dependent and is disrupted by in vivo blockade of NMDA receptors (Hahm et al., 1991). To investigate a possible mechanism whereby blockade of postsynaptic NMDA receptors in the lateral geniculate nucleus (LGN) results in changes in the size and position of presynaptic axon arbors, we tested the role of the diffusible messenger nitric oxide (NO) in the development of the retinogeniculate pathway. We found previously that NO synthase (NOS) is transiently expressed in LGN cells during the refinement of retinogeniculate projections . In this study, treatment with N G -nitro-L-arginine (L-NoArg), an arginine analog that inhibits NOS, during the third and fourth postnatal weeks resulted in an overall pattern of sublamination that was significantly reduced compared with normal and control animals. Single retinogeniculate axon arbors were located in the middle of eye-specific layers rather than toward the inner or outer half as in normal or control animals. The effect of NOS inhibition was not a consequence of the hypertensive effect of L-NoArg. In contrast to the effect of L-NoArg on the formation of ON/OFF sublaminae, treatment with L-NoArg during the first postnatal week did not disrupt the formation of eye-specific layers. Biochemical assays indicated significant inhibition of NOS during both treatment periods. These data suggest that NO acts together with NMDA receptors in activity-dependent refinement of connections during a specific phase of retinogeniculate development. Key words: diffusible messenger; visual system; lateral geniculate nucleus (LGN); pattern formation; eye-specific layers; ON/ OFF sublaminae; neuronal activityThe precise pattern of connections underlying adult visual processing in mammals arises from the refinement of less specific connectivity present early in development. The mechanisms by which diffuse connections are refined rely at least in part on neuronal activity. In the ferret, retinogeniculate connections are refined in two distinct phases. During the first postnatal week, retinal axons within the lateral geniculate nucleus (LGN) segregate into eye-specific layers (Linden et al., 1981). During the third and fourth postnatal weeks, afferents to the A and A1 layers, which receive input from the contralateral and ipsilateral eye, respectively, further segregate into sublaminae. The inner sublamina receives inputs from on-center retinal ganglion cells, whereas the outer sublamina receives inputs from off-center retinal ganglion cells (Stryker and Zahs, 1983;Hahm and S...

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“…The first synaptically connected circuits that appear in the developing IPL form between amacrine and RGCs (Greiner and Weidman, 1981;Mey and Thanos, 1992;Karne et al, 1997). There is evidence of functional cholinergic synapses, although most of these synapses are GABAergic.…”

Section: Cholinergic Network In the Developing Vertebrate Retinamentioning

confidence: 99%

The role of nAChR‐mediated spontaneous retinal activity in visual system development

Feller

2002

J. Neurobiol.

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ABSTRACT:In the developing vertebrate retina, nAChR synapses are among the first to appear. This early cholinergic circuitry plays a key role in generating "retinal waves," spontaneously generated waves of action potentials that sweep across the ganglion cell layer. These retinal waves exist for a short period of time during development when several circuits within the visual system are being established. Here I review the cholinergic circuitry of the developing retina and the role these early circuits play in the development of the retina itself and of retinal projections to the lateral geniculate nucleus of the thalamus.

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Histogenesis of the ferret retina

Cited by 81 publications

References 8 publications

Stable rAAV-mediated transduction of rod and cone photoreceptors in the canine retina

Stable rAAV-mediated transduction of rod and cone photoreceptors in the canine retina

A Role for Nitric Oxide in the Development of the Ferret Retinogeniculate Projection

The role of nAChR‐mediated spontaneous retinal activity in visual system development

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