In the frog Hyla moorei we have estimated there to be between approximately 450,000 and 750,000 cells in the retinal ganglion cell layer. Optic axon counts and retrograde transport of horseradish peroxidase (HRP) indicated that 72-76% of these were ganglion cells. Cells of this type were distributed as a temporally situated area centralis within a horizontal visual streak. Cell and optic axon counts showed that there was an approximately 40% loss of ganglion cells during optic nerve regeneration. Ganglion cells appeared chromatolysed by 6-8 days after an extracranial nerve crush but there was no indication of cell death until 15 days. By this stage anterograde transport of HRP indicated that axons had reached the chiasma. Death was first seen in the area centralis, extended along the streak, and finally was observed in the periphery by 65 days; cell counts demonstrated that at this time the wave of death was almost complete. We have previously shown by electrophysiological visual mapping (Humphrey and Beazley, '82) and confirmed in this study that visuotectal projections were retinotopically organized during regeneration. Multiunit receptive fields were initially large but progressively refined starting in nasal field (temporal retina) to restore a normal projection. The similar sequences whereby the visuotectal projection became refined and death took place in the retinal ganglion cell layer suggested that death may be related to a process of organization within the regenerating projection. In normal animals primary visual pathways revealed by anterograde transport of HRP were essentially similar to those of Rana pipiens and R. esculenta. Regenerating axons generally remained within optic pathways. Exceptions were a retinoretinal projection which was not completely withdrawn even after 1,028 days and a direct projection to the ipsilateral tectum via an inappropriate part of the optic tract.

Key Points The hepcidin inhibitor NOX-H94, a structured mirror-image RNA oligonucleotide, and its in vitro and in vivo characterization are described. First published hepcidin inhibitor that entered clinical trials for the treatment of anemia due to functional iron deficiency.

No abstract

1. Retinal ganglion cells were recorded extracellularly in the intact eye of anesthetized adult cats. The effects of acetylcholine (ACh), the muscarinic antagonist scopolamine (Sco), the nicotinic antagonist dihydro-beta-erythroidine (DBE), and the acetylcholinesterase inhibitor physostigmine (Phy) on maintained and light-evoked ganglion cell discharge was examined using iontophoresis techniques. 2. A monoclonal antibody directed against the ACh synthesizing enzyme choline acetyltransferase (ChAT) was used to label cholinergic cells in retinal wholemounts. The topographical distribution of these cells was studied. 3. Intracellular filling with the fluorescent dye lucifer yellow (LY) was performed to identify the dendritic morphology of putative cholinergic neurons. 4. ACh increased and Sco decreased neuronal activity of all brisk ganglion cell types under all stimulus conditions tested in this study. The action of ACh was abolished during simultaneous application of Sco. 5. DBE raised the firing rate of ON-center brisk cells and decreased activity of OFF-center brisk cells. Again there was no difference under different stimulus conditions. During DBE application the ACh action on OFF-center cells was completely blocked. The ACh action on ON-center cells was diminished. 6. Phy prolonged and enhanced ACh action on all ganglion cell types. During simultaneous stimulation of the receptive-field center and the surround, Phy caused an activity shift in favor of the center response. 7. Immunocytochemical staining revealed two populations of amacrine cells, one in the inner nuclear layer, and the other in the ganglion cell layer. Their total density increased from 250 cells/mm2 in the periphery to 2,700 cells/mm2 in the central area. Analysis of the distribution pattern indicated a functional independence of the two subpopulations. 8. The dendritic morphology of putative cholinergic amacrine cells in the cat retina resembled that of rabbit and rat "starburst" amacrines, which are known to be cholinergic. 9. The possible function of cholinergic amacrine cells in the cat retina is discussed in view of the present findings and compared with results from other mammalian species.

A wide variety of retinal pathology is associated with an increase in Müller glial cell expression of glial fibrillary acidic protein (GFAP). In this study the time course and spatial spread of the Müller cell GFAP response following argon laser photocoagulation lesions was examined in wholemounted rabbit retina. At 24 hours single focal lesions were surrounded by GFAP positive Müller cell end feet which declined in density with distance but extended as far as 2-3 mm from the lesion. The Müller cell reaction reached a maximal spread of 4-5 mm at 14 to 21 days and had started to contract by 30 days, leaving a core of GFAP positive processes immediately around the lesion site at 60 days. This zone of spread was much larger than the area of disrupted pigment epithelium. Isodensity plots did not reveal any correlation with the trajectory of retinal ganglion cell axons. The spread of reaction was more confined for lesions within the visual streak than in the dorsal or ventral retinal periphery. Multiple lesions within a focal region of retina resulted in a greater density of GFAP reactive end feet with a corresponding greater spread. However, when five to ten lesions were made in a horizontal row, the Müller cells over the entire retina became GFAP immunoreactive. This pan-retinal reaction took several days to spread, peaked at 7-14 days, and contracted back to the primary lesion sites by 2 months. This spread of Müller cell reactivity may be triggered by the diffusion of substances released by injury or it may be due to direct cellular communication. The extensive indirect effect on Müller cells of laser irradiation might be an important component of the clinical effect of laser photocoagulation and indicates a long distance communication mechanism between retinal glia which is poorly understood. This study also shows the importance of the time at which the Müller cell response is assessed.