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D A Redburn

Publications and source records attributed to D A Redburn.

At least 55 records · Page 3Linked to original sources

A tonic gamma-aminobutyric acid-mediated inhibition of cholinergic amacrine cells in rabbit retina.

Using the in vivo rabbit eyecup, we have studied the light-evoked release of acetylcholine (ACh) which is presumed to indicate the activity of cholinergic amacrine cells. Gamma-Aminobutyric acid (GABA) inhibited the light-evoked release of ACh (IC50 congruent to 1 mM), but the GABA antagonists bicuculline (5 micro M) and picrotoxin (20 micro M) potentiated the light-evoked release and markedly increased the resting release of ACh. This bicuculline/picrotoxin-evoked release was calcium dependent and the effects of bicuculline, but not picrotoxin, were blocked by muscimol, a potent GABA agonist. Muscimol also inhibited the light-evoked release of ACh (IC50 less than 1 micro M) and was at least 1000 times more potent than GABA. Nipecotic acid (1 mM), a GABA transport blocker, also inhibited the light-evoked release of ACh, but the effect was slow in onset and recovery was prompt. We conclude that the cholinergic amacrine cells of rabbit retina are inhibited by GABA. The relatively weak action of GABA, compared to muscimol, may be due to the presence of avid GABA transport systems. We ascribe the excitatory effects of bicuculline and picrotoxin to the antagonism of endogenous GABA, suggesting that the cholinergic cells are influenced by a tonic release of GABA. This is consistent with the effects of nipecotic acid. Although we are unable to specify the synaptic arrangements involved, we suggest that the most likely interaction is directly between GABA amacrine cells and the cholinergic amacrine cells and/or their presumed bipolar cell inputs.

Acetylcholine↗

Localization of kainic acid-sensitive cells in mammalian retina.

Short-term (15 minutes) in vitro exposure to kainic acid (KA), a rigid structural analog of L-glutamic acid (Glu), caused two morphologically distinct neuronal lesions in retinas of several species. In rabbit retina, one type of lesion was characterized by rapid swelling after exposure to low concentrations of KA (10(-4)M). This lesion was observed in elements of both plexiform layers and, more specifically, in cell bodies and neurites of horizontal cells that contact cones. A few cell bodies from the amacrine cell layer showed some limited swelling. The swelling was completely blocked when sodium was removed from the incubation medium. The second type of lesion was generally seen after longer exposures of after exposure to higher concentrations of KA and was evidenced by degeneration of neurons in the amacrine and ganglion cell layers. One exception was noted in that a few cells from the ganglion cell layer degenerated even under low exposure conditions. The second type of lesion was not blocked by removal of sodium ions. Photoreceptor cells appeared resistant to all effects of KA. The results suggest that a correlation may exist between certain KA-induced lesions of the retina and putative glutamoreceptive neurons. At the same time, the two types of retinal lesions produced by KA are morphologically and chemically differentiable and may be useful in elucidating the differences between specific, Glu-related toxicity and nonspecific toxicity of KA.

Animals↗

3H-muscimol binding in synaptosomal fractions from bovine and developing rabbit retinas.

Bovine and rabbit retina synaptosomal fractions bind the potent and specific GABA agonist, [3H]-muscimol with high affinity and limited capacity. The high degree of pharmacological specificity and the subcellular distribution of these binding sites are similar to those reported for [3H]-GABA binding sites. These observations suggest that these sites represent the recognition sites for GABA receptors. The specific binding of [3H]-muscimol in retinal homogenates from different aged rabbits reveal a distinct developmental profile with a fivefold to six fold increase in binding between days 5 and 13. Thus, it appears that GABA receptor development continues after eye opening in rabbits (day 9-10) and that receptor maturation is delayed by at least two to three days with respect to published of GABA uptake and evoked release.

Animals↗

GABA and glutamate as retina neurotransmitters in rabbit retina.

In summary, both glutamate and GABA appear to be functional neurotransmitters in the inner plexiform layer of the rabbit retina. Autoradiograph localization suggests they are both subpopulations of amacrine cells which are found primarily in the amacrine cell layer, although some appear as displaced amacrines in the ganglion cell layer. The characteristics of these two transmitter systems are similar to those described in brain including systems for transport, release and receptor binding. There is considerable evidence that GABAnergic cells may be responsible for the specificity of on-center ganglion cells through inhibitory modulation of cholinergic transmission. The role of glutamate is much more speculative at this point, however, it is suggested that the excitatory input to the GABAnergic neurons may be mediated by glutaminergic transmission.

Animals↗

Bacterial collagenase. Proposed adjunct to vitrectomy with membranectomy.

Clostridiopeptidase A digested preretinal cicatricial tissue without causing morphological alteration of normal retina during a 30-minute incubation in the rabbit. Light and transmission electron microscopy were used to determine effects on the inner limiting membrane and retinal ganglion and Müller's cells and to evaluate enzyme digestion of preretinal scarring. Removal of the injected collangenase by vitrectomy resulted in normal electroretinograms and retinal morphology 48 hours postoperatively. If the enzyme was left in the eye for 24 hours, lens opacities, partial erosion of the inner limiting membrane, and extensive hemorrhage resulted. The specificity of action of the collagenase is due to the high degree of purity of the enzyme used and a substantial biochemical difference between scar collagen and basement membrane collagen. The injection of purified collagenase capable of digesting vitreal scar tissue while leaving the retina undamaged could represent a new approach to vitrectomy, specifically to facilitate certain cases of membranectomy.

Animals↗

The effects of intravitreal irrigation during vitrectomy on the electroretinogram.

Intravitreal irrigation with Balanced Salt Solution Plus (BSS Plus) produced less decrease in b-wave amplitude than either normal saline solution or Balanced Salt Solution. BSS Plus was more suitable for intravitreal irrigation because it contained the appropriate bicarbonate, pH, and ionic composition necessary for maintenance of normal retinal electrical activity, and it contained glutathione, which is necessary for maintenance of endothelial cell adenosine triphosphatase and for protection against free radical damage and oxidative stress.

Animals↗

Isolation of synaptosomal fractions from rabbit retina.

Homogenization of rabbit retina in isotonic sucrose and differential rate centrifugation yielded two morphologically distinct synaptosomal fractions. One fraction was enriched in photoreceptor cell synaptosomes; the second fraction contained small synaptosomes derived from conventional sized synapses most abundant in the inner plexiform layer. Attempts to further purify these fractions using a variety of density gradients proved unsuccessful due to poor viability of photoreceptor cell synaptosomes. The synaptosomes prepared by our method are functionally stable as they demonstrate high affinity uptake for putative retinal neurotransmitters, neurotransmitter-sensitive adenylate cyclase activity, and calcium-dependent, potassium-stimulated release of [14C]GABA and [3H]dopamine.

Animals↗