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Neuropeptides and retinal development
Different peptidergic systems have been investigated with some detail during retinal development, including substance P (SP), vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP) and somatostatin (SRIF). Concerning possible developmental actions of neuropeptides, VIP and PACAP exert protective and growth-promoting actions that may sustain retinal neurons during their development. In addition, the presence of transient SRIF expressing cells and recent observations in SRIF receptor knock out mice indicate variegated roles of this peptide in the development of the retina and of retinofugal projections. Finally, recent studies have shown that, in the developing rabbit retina, changes in the expression pattern of SP receptors are accompanied by modifications of SP physiological effects, indicating that retinal circuits where SP is involved are likely to function in a substantially different manner before the retina becomes involved in the processing of visual stimuli. SP neurotransmission in the immature retina may subserve developmental events, and SP is likely to represent an important developmental factor for the maturation of retinal neurons and circuitries
Localization and function of GABA transporter 1 in the retina
Plasma membrane transporters, located in the presynaptic terminal and/or surrounding glial cells, terminate synaptic transmission by operating rapid, high affinity uptake of the neurotransmitter from the synaptic cleft. Pharmacological blockade of transporters increases extracellular neurotransmitter levels and prolongs transmitter exposure to the receptors. GABA transporters (GATs) belong to the Na+ and Cl--dependent transporter family. Four GATs have been isolated and cloned in mammals. Of them, GAT-1 and GAT-3 are expressed in the retina. GAT-1 has a widespread distribution to different retinal cell types, but it is prominently expressed in amacrine cells of all vertebrate species studied to date. There are some species differences in the expression patterns of GAT-1 in the retina. It is expressed by horizontal cells in non-mammalian but not in mammalian retinas, and it is expressed in Müller glial cells of rats and guinea pigs, but not of rabbits and primates.
Functionally, GAT-1, together with GAT-3, regulates the extracellular GABA levels in the retina, thereby determining the level of inhibitory interactions and affecting visual processing in the retinal pathways. GAT-1 may interact with GABAC receptors on bipolar cell terminals and influence ganglion cell responses. It may also interact with GABAB receptors in the regulation of retinal waves of spontaneous activity which are known to play critical roles during development of the visual system. Other important functional actions are exerted by GAT-1 through reversed GABA transport. These include GABA release by cholinergic/GABAergic starburst amacrine cells and GABA release during early retinal development
Vasoactive intestinal polypeptide-containing cells in in the rabbit retina: Immunohistochemical localization and quantitative analysis
Vasoactive intestinal polypeptide (VIP) possesses neuroactive properties in the nervous system. In this study we characterized VIP immunoreactive neurons in the rabbit retina to provide a basis for a better understanding of the role of this peptide in retinal functions and to further define the morphology of wide-field amacrine cells. VIP immunoreactivity was demonstrated in colchicine-treated retinas. Immunolabeling was observed in amacrine cells located in the proximal inner nuclear layer and, occasionally, in the ganglion cell layer and inner plexiform layer (IPL). Varicose fibers were distributed in laminae 1, 3, and 5 of the IPL. The distribution of VIP immunoreactive cells showed a peak of approximately 50 cells/mm2 in the visual streak and minimum values of approximately 12 cells/mm2 in the peripheral retina. The total number of VIP immunopositive neurons was estimated to be about 11,000. Cell body diameters in the visual streak (8-9 microns) were slightly smaller than those measured in the dorsal or in the ventral retina (9-10 microns). The distribution of nearest neighbor distances (approximately 109 microns in the visual streak and approximately 99 microns in the peripheral retina) showed that VIP immunoreactive neurons were nonrandomly spaced. Labeled neurons emitted one to three thick primary processes, arborizing in secondary processes and collaterals rich in varicosities; these processes often crossed among different IPL laminae. Arborization fields of individual cells overlapped extensively. In the dorsal retina, estimated areas of single arborization fields were larger and processes had lower branching frequency than in the visual streak and in the ventral retina. On the whole, VIP immunoreactive amacrine cells gave rise to a loose meshwork of fibers in the IPL. These characteristics indicate VIP is contained in a class of wide-field amacrine cells and is likely to be involved in widespread regulatory or modulatory functions rather than in the direct transmission of visual information through the retina
The neuropeptide systems and their potential role in the treatment of mammalian retinal ischemia: a developing story
The multiplicity of peptidergic receptors and of the transduction pathways they activate offers the possibility of
important advances in the development of specific drugs for clinical treatment of central nervous system disorders.
Among them, retinal ischemia is a common clinical entity and, due to relatively ineffective treatment, remains a common
cause of visual impairment and blindness. Ischemia is a primary cause of neuronal death, and it can be considered as a sort
of final common pathway in retinal diseases leading to irreversible morphological damage and vision loss. Neuropeptides
and their receptors are widely expressed in mammalian retinas, where they exert multifaceted functions both during
development and in the mature animal. In particular, in recent years somatostatin and pituitary adenylate cyclase
activating peptide have been reported to be highly protective against retinal cell death caused by ischemia, while data on
opioid peptides, angiotensin II, and other peptides have also been published. This review provides a rationale for
harnessing the peptidergic receptors as a potential target against retinal neuronal damages which occur during ischemic
retinopathies
Postnatal development of tyrosine hydroxylase immunoreactive amacrine cells in the rabbit retina. II. Quantitative analysis
Tyrosine hydroxylase (TH)-immunoreactive (IR) amacrine cells of the rabbit retina mature during the first four postnatal weeks, and their cellular development is described in the preceding paper (Casini, G., and N.C. Brecha, J. Comp. Neurol. 326:283-301, 1992). The present investigation is a quantitative analysis of the postnatal development of the TH-IR amacrine cell population. TH-IR amacrine cells gradually increase in size from birth (soma area of 44.7 +/- 12.4 microns2, mean +/- standard deviation) to adulthood (144.2 +/- 28.0 microns2). Cell density slightly increases from postnatal day (PND) 0 (41.9 +/- 9.5 cells/mm2) to PND 6 (47.2 +/- 7.2 cells/mm2), then markedly decreases from PND 6 to adulthood (17.8 +/- 5.3 cells/mm2) as a consequence of retinal growth. TH-IR cell number almost doubles from PND 0 (about 4,100 cells/retina) to adulthood (about 7,850 cells/retina). The increase in the total number of TH-IR amacrine cells can be explained by the generation of new TH-IR cells in the inner nuclear layer, a delay in the expression of the TH phenotype after neurogenesis by cells committed to be dopaminergic, or the acquisition of this dopaminergic phenotype by uncommitted cells. The development of the TH-IR amacrine cell mosaic was assessed by an evaluation of the distribution of nearest neighbor distances of TH-IR cells. There is a poor correlation between this distribution and a theoretical nonrandom distribution before PND 12. After this age, the nearest neighbor distance distribution shifts towards a nonrandom distribution, and is similar to that of the TH-IR amacrine cell population in the adult retina. The establishment of the TH-IR amacrine cell population mosaic is likely to be achieved through different interacting events, including intrinsic (e.g., genetic) factors, environmental influences, and nonuniform retinal growth. Overall, the population parameters analyzed in the present study approach adult values about the time of eye opening (PND 12) and they reach adult values by PND 26
Recent advances in cellular and molecular aspects of mammalian retinal ischemia
Retinal ischemia is a common clinical entity and, due
to relatively ineffective treatment, remains a common
cause of visual impairment and blindness. Generally,
ischemic syndromes are initially characterized by low
homeostatic responses which, with time, induce injury
to the tissue due to cell loss by apoptosis. In this respect,
retinal ischemia is a primary cause of neuronal
death. It can be considered as a sort of final common
pathway in retinal diseases and results in irreversible
morphological and functional changes. This review
summarizes the recent knowledge on the effects of
ischemia in retinal tissue and points out experimental
strategies/models performed to gain better comprehension
of retinal ischemia diseases. In particular, the
nature of the mechanisms leading to neuronal damage
(i.e., excess of glutamate release, oxidative stress and
inflammation) will be outlined as well as the potential
and most intriguing retinoprotective approaches and
the possible therapeutic use of naturally occurring
molecules such as neuropeptides. There is a general
agreement that a better understanding of the fundamental
pathophysiology of retinal ischemia will lead to better management and improved clinical outcome. In
this respect, to contrast this pathological state, specific
pharmacological strategies need to be developed
aimed at the many putative cascades generated during
ischemia
Postnatal development of tyrosine hydroxylase immunoreactive amacrine cells in the rabbit retina. I. Morphological characterization
The present and accompanying (Casini, G., and N.C. Brecha, J. Comp. Neurol. 326:302-313, 1992) papers investigate the postnatal development of tyrosine hydroxylase (TH)-immunoreactive (IR) amacrine cells in the rabbit retina. This study is focused on a detailed analysis of the patterns of cellular growth and differentiation of TH-IR amacrine cells, which serve as a model to gain insights into the mechanisms underlying developmental changes associated with the maturation of amacrine cells. Faintly staining TH-IR neurons are present in the proximal inner nuclear layer of newborn retinas. They are characterized by a large nucleus and usually a single primary process lacking varicosities. At postnatal day (PND) 6, TH-IR processes display more complex morphological characteristics, including a few varicosities, and second- and third-order ramifications. Growth cones are often seen. At PNDs 10 and 12 (eye opening), TH-IR cells have general morphological characteristics similar to adult TH-IR amacrines. They display 2-5 primary processes, which start forming a complex network of fibers in lamina 1 of the inner plexiform layer (IPL). TH-IR processes are also present in lamina 3 and rarely in lamina 5 of the IPL. Many fibers ending in growth cones are observed. In addition, very rare, thin TH-IR fibers are present in the outer plexiform layer. At PND 19, TH-IR fibers form a complex, dense network in lamina 1 of the IPL, and loose networks in laminae 3 and 5. Growth cones are not observed at this age. At PND 26, a few "ring-like" structures formed by TH-IR fibers in lamina 1 of the IPL are observed for the first time. In adult retinas, the "ring-like" structures are more numerous than at PND 26. A second, rare type of TH-IR cell ("type B") is encountered in all retinal regions beginning at PND 10. These cells are characterized by weak immunostaining and a small soma size. The present findings show that a significant differentiation of TH-IR neurons occurs during the first 10-12 PNDs. Eye opening is an important period for the maturation of TH-IR amacrines and, more generally, for the maturation of the IPL
Pigeons with ablated pyriform cortex home from familiar but not from unfamiliar sites
Homing behavior was tested in pigeons
(Columba livia) after removing a portion of the ventrolateral
telencephalon, which receives extensive projections from the
olfactory bulb and is comparable with the mammalian pyriform
cortex. Ablated pigeons show unaffected cardiac responses
to odorous stimuli but altered homing behavior. After
the operation, the birds were trained by repeated flock releases
along with control birds from a site 40 km from the loft. After
being released singly from this familiar site, the ablated birds
turned out to be unaffected by the operation. In releases from
two unfamiliar sites, ablated birds, unlike control birds, were
not homeward oriented and were mostly lost. The ablation of
the pyriform cortex has the same effect on homing behavior as
olfactory deprivation. It can be concluded that the pyriform
cortex plays an important role in the specific mechanisms
linking olfactory inputs with the navigational response
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