Subsurface cisterns in the vertebrate retina

Structures identified as subsurface cisterns (SSC's) were found in retinal neurons and their processes in the Western grey squirrel, the California and 13-line ground squirrels, the South African clawed toad, and the domestic cat. The SSC's are located in amacrine, bipolar, and ganglion cells; they are connected with the rough endoplasmic reticulum and are associated with specific membrane specializations. SSC's were not seen in the Müller cells, an observation which agrees with earlier reports that these organelles do not exist in glial cells.     

GABAC receptors in the vertebrate retina

In the central nervous system (CNS), the inhibitory transmitter GABA interacts with three subtypes of GABA receptors, type A, type B, and type C. Historically, GABA receptors have been classified as either the inotropic GABA_A receptors or the metabotropic GABA_B receptors. Over the past 10 yr, studies have shown that a third class, called the GABA_C receptor, also exists. GABA_C receptors are found primarily in the vertebrate retina and to some extent in other parts of the CNS. Although GABA_A and GABA_C receptors both gate chloride channels, they are pharmacologically, molecularly, and functionally distinct. The ρ subunit of the GABA_C receptor, which has about 35% amino acid homology to GABA_A receptor subunits, was cloned from the retina and, when expressed inXenopus oocytes, has properties similar to retinal GABA_C receptors. There are probably distinct roles for GABA_C receptors in the retina, because they are found on only a subset of neurons, whereas GABA_A receptors are ubiquitous. This article reviews recent electrophysiological and molecular studies that have characterized the unique properties of GABA_C receptors and describes the roles that these receptors may play in visual information processing in the retina.     

Depletion of taurine in the adult rat retina

Taurine is the major free amino acid of the vertebrate retina. Treatment of rats with guanidinoethyl sulfonate (GES), a taurine analogue which competes with taurine for transport sites, leads to depletion of 60% of retinal taurine with little effect on other free amino acids. Supplementation of the diet with 0.3% taurine gives partial protection against depletion, confirming that taurine-GES competition underlies part of the effects. The magnitude of the depletion suggests the importance of taurine transport across the blood-retinal barrier for the maintenance of retinal taurine levels.     

Lactoseries carbohydrate epitopes in the vertebrate retina

The distribution of N-acetyl-lactosamine (NALA), a cell-surface carbohydrate epitope of the lactoseries, has been studied in the retina of representative species of all vertebrate classes by light microscope immunohistochemistry. In only some species of different classes (fish, amphibia and mammals) was NALA expression detected, and in these animals the distribution showed profound interspecies variability. In fishes and amphibia in which NALA was present, patterns ranged from single immunopositive cells to homogeneous labelling of cell layers. In mammals, NALA was found only in retinas that are cone dominated (tree squirrel and primates). In the tree squirrel, there was a dense cellular staining of the photoreceptor cell layer; whereas in primates, the carbohydrate epitope occur red only on some photoreceptor cells. From these receptor cells, positi ve axons could be traced to the inner plexiform layer. In spite of the profound interspecies differences, NALA is not randomly expressed, as its exclusive expression in mammals with cone- dominated vision indicates. The suggestion of a functional relevance for NALA glycosylation of retinal cells is supported by the labelling pattern for HNK-1 in these species, which was different from the pattern found in rod-dominated mammalian retinas. This revised version was published online in November 2006 with corrections to the Cover Date.     

Cell death in the developing vertebrate retina

Programmed cell death occurs naturally, as a physiological process, during the embryonic development of multicellular organisms. In the retina, which belongs to the central nervous system, at least two phases of cell death have been reported to occur during development. An early phase takes place concomitant with the processes of neurogenesis, cell migration and cell differentiation. A later phase affecting mainly neurons occurs when connections are established and synapses are formed, resulting in selective elimination of inappropriate connections. This pattern of cell death in the developing retina is common among different vertebrates. However, the timing and magnitude of retinal cell death varies among species. In addition, a precise regulation of apoptosis during retinal development has been described. Factors such as neurotrophins, among many others, and electrical activity influence the survival of retinal cells during the course of development. In this paper, we present a summary of these different aspects of programmed cell death during retinal development, and examine how these differ among different species.     

High-affinity taurine uptake in developing retina

A specific system for taurine transport is present at the early stages of development in both chick and rat retinas. The results obtained with taurine analogs indicate a high degree of specificity of taurine uptake. Two transport systems were detected for the adult rat retina: a high-affinity (K _m 21 M) and a low-affinity transport system (K _m 312 M). On the other hand, in the adult chick retina, only a low-affinity transport system (K _m 580 M) could be detected. Nevertheless, embryo chick retina accumulated [³H]taurine by two different kinetic mechanisms withK _m s of 242 M and 21 M for the low- and high-affinity processes, respectively. Taurine uptake systems were absolutely Na⁺ dependent. The sodium-dependence curve for taurine uptake was sigmoid. These mechanisms appear not to be mediated by a Na⁺ cotransport system. In spite of the differences observed in taurine uptake in both species, in each of them it closely parallels the changes brought about by the morphological and functional maturation of the retina.     

The presence of dopamine-β-hydroxylase-like enzyme in the vertebrate retina

An analysis of the dopamine-β-hydroxylase activity in various ocular tissues revealed low enzymatic activity in all the retinas analysed. Bovine and monkey retinas had the highest enzyme activity. The enzyme is also present in bovine optic nerve and pigment epithelium/choroid complex, and low levels are present in the vitreous. Immunohistochemical analysis of various retinas with an antiserum raised to bovine adrenal dopamine-β-hydroxylase-showed positive staining only in monkey and bovine retinas. In both instances dopamine-β-hydroxylase immunoreactivity was associated with cells in the ganglion cell layer. These cells are probably ganglion cells since some positive staining was also observed in the bovine optic nerve. Autoradiographical analysis of the uptake of [³H]noradrenaline showed that grains were associated with some structures in the ganglion cell layer. A single prominent layer of terminals at the junction of the inner nuclear and inner plexiform layer of the bovine retina was also apparent. This was considered to be due to [³H]noradrenaline accumulation by dopaminergic amacrine cells. The results suggest that a small number of noradrenergic and/or adrenergic ganglion cells may exist in certain retinas.     

Response analysis of vertebrate retina

In a recent work (Ouztöreli, 1980) a mathematical model for studying the neural activities in a vertebrate retina has been investigated, where the basic network contains five interconnected neurons: a receptor cell, a bipolar cell, a horizontal cell, an amacrine cell, and a retinal ganglion cell. More recently, in (Ouztöreli and O'Mara, 1980) the basic network has been extended to a larger network containing twelve neurons. In both of these works, the performances of the basic and extended models were discussed under different structural and processing conditions with constant inputs by using the results of one of our earlier work (Ouztöreli, 1979). In the present paper we investigate by simulations the responses of the basic retinal network to piecewise constant and periodic inputs. The step and frequency responses of the extended retinal network will be discussed in a forthcoming paper.This work was partially supported by the Natural Sciences and Engineering Research Council of Canada under Grant A-4345 through the University of alberta     

Ultrastructural localization of rhodopsin in the vertebrate retina

Early work by Dewey and collaborators has shown the distribution of rhodopsin in the frog retina. We have repeated these experiments on cow and mouse eyes using antibodies specific to rhodopsin alone. Bovine rhodopsin in emulphogene was purified on an hydroxyapatite column. The purity of this reagent was established by spectrophotometric criteria, by sodium dodecyl sulfate (SDS) gel electrophoresis, and by isoelectric focusing. This rhodopsin was used as an immunoadsorbent to isolate specific antibodies from the antisera of rabbits immunized with bovine rod outer segments solubilized in 2% digitonin. The antibody so prepared was shown by immunoelectrophoresis to be in the IgG class and did not cross-react with lipid extracts of bovine rod outer segments. Papain-digested univalent antibodies (Fab) coupled with peroxidase were used to label rhodopsin in formaldehyde-fixed bovine and murine retinas. In addition to the disk membranes, the plasma membrane of the outer segment, the connecting cilium, and part of the rod inner segment membrane were labeled. We observed staining on both sides of the rod outer segment plasma membrane and the disk membrane. Discrepancies were observed between results of immunolabeling experiments and observations of membrane particles seen in freeze-cleaved specimens. Our experiments indicate that the distribution of membrane particles in freeze cleaving experiments reflects the distribution of membrane proteins. Immunolabeling, on the other hand, can introduce several different types of artifact, unless controlled with extreme care.     

A dynamic model of the vertebrate retina

In this paper a mathematical model of the retina was proposed to clarify the spatio-temporal information processing mechanism in the retina of vertebrates. In order to explain spatio-temporal characteristics of an on-center receptive field of a ganglion cell, excitatory and inhibitory cell layers were introduced of which time lags increased with the lateral distance from a point of stimulation. The characteristics of this model were found to agree well with the physiological data: e.g., this model shows on-response to the input stimulus given on the center, off-response to the input on the surround, and on-off response to the input on the border between on- and off-response regions of the on-center field.     

Progranulin regulates neurogenesis in the developing vertebrate retina

We evaluated the expression and function of the microglia‐specific growth factor, Progranulin‐a (Pgrn‐a) during developmental neurogenesis in the embryonic retina of zebrafish. At 24 hpf pgrn‐a is expressed throughout the forebrain, but by 48 hpf pgrn‐a is exclusively expressed by microglia and/or microglial precursors within the brain and retina. Knockdown of Pgrn‐a does not alter the onset of neurogenic programs or increase cell death, however, in its absence, neurogenesis is significantly delayed—retinal progenitors fail to exit the cell cycle at the appropriate developmental time and postmitotic cells do not acquire markers of terminal differentiation, and microglial precursors do not colonize the retina. Given the link between Progranulin and cell cycle regulation in peripheral tissues and transformed cells, we analyzed cell cycle kinetics among retinal progenitors following Pgrn‐a knockdown. Depleting Pgrn‐a results in a significant lengthening of the cell cycle. These data suggest that Pgrn‐a plays a dual role during nervous system development by governing the rate at which progenitors progress through the cell cycle and attracting microglial progenitors into the embryonic brain and retina. Collectively, these data show that Pgrn‐a governs neurogenesis by regulating cell cycle kinetics and the transition from proliferation to cell cycle exit and differentiation. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 77: 1114–1129, 2017     

Cytoprotection by endogenous zinc in the vertebrate retina

Our recent studies have shown that endogenous zinc, co‐released with glutamate from the synaptic terminals of vertebrate retinal photoreceptors, provides a feedback mechanism that reduces calcium entry and the concomitant vesicular release of glutamate. We hypothesized that zinc feedback may serve to protect the retina from glutamate excitotoxicity, and conducted in vivo experiments on the retina of the skate (Raja erinacea) to determine the effects of removing endogenous zinc by chelation. These studies showed that removal of zinc by injecting the zinc chelator histidine results in inner retinal damage similar to that induced by the glutamate receptor agonist kainic acid. In contrast, when an equimolar quantity of zinc followed the injection of histidine, the retinal cells were unaffected. Our results are a good indication that zinc, co‐released with glutamate by photoreceptors, provides an auto‐feedback system that plays an important cytoprotective role in the retina.

     

Phosphoinositide 3-kinase signaling in the vertebrate retina

The phosphoinositide (PI) cycle, discovered over 50 years ago by Mabel and Lowell Hokin, describes a series of biochemical reactions that occur on the inner leaflet of the plasma membrane of cells in response to receptor activation by extracellular stimuli. Studies from our laboratory have shown that the retina and rod outer segments (ROSs) have active PI metabolism. Biochemical studies revealed that the ROSs contain the enzymes necessary for phosphorylation of phosphoinositides. We showed that light stimulates various components of the PI cycle in the vertebrate ROS, including diacylglycerol kinase, PI synthetase, phosphatidylinositol phosphate kinase, phospholipase C, and phosphoinositide 3-kinase (PI3K). This article describes recent studies on the PI3K-generated PI lipid second messengers in the control and regulation of PI-binding proteins in the vertebrate retina.     

Target cells of vitamin D in the vertebrate retina

Using PAP technique, cellular localization of vitamin D-dependent calcium-binding protein (D-CaBP) was investigated in vertebrate retina with monospecific antisera against chick duodenal D-CaBP. In the chick retina, the receptor cells were positive. In the inner nuclear layer, horizontal cells and some bipolar cells were also positive. Some amacrine cells as well as different levels of the inner plexiform layer were also positive for D-CaBP. A few interspersed ganglion cells were positive but their axons forming the optic tract were negative. Müller's cells were negative. In 1-day-old chicks and 4-week-old rachitic chicks there was paucity and absence, respectively, of D-CaBP staining in horizontal cells. In the mouse, rat, and rabbit the receptors had only trace amounts of reaction product in their outer segment and pedicle. Horizontal cells were densely positive throughout their cellular body and processes. Some amacrine cells in the inner nuclear layer were positive. In the mouse and rat three horizontal levels of the outer plexiform layer were very prominent because of their dense staining for D-CaBP. Many ganglion cells were also positive along with their axons forming the optic nerve. In the rabbit, no positive layers were seen in the inner plexiform layer, and ganglion cells with their fibers were negative. In the frog retina there were smaller amounts of D-CaBP in the receptor cells and horizontal cells than that of the chick retina. Also, the fibers of the ganglionic cells were positive for D-CaBP. In all species studied, some amacrine cells were stained for D-CaBP. Because of its possible roles in membrane calcium transport and intracellular Ca++ regulation, it has perhaps similar functions in these positive cells. The synthesis of D-CaBP is dependent upon vitamin D. These positive cells are thus target cells of vitamin D.     

Synapsins in the vertebrate retina: absence from ribbon synapses and heterogeneous distribution among conventional synapses

The vertebrate retina contains two ultrastructurally distinct types of vesicle-containing synapses: conventional synapses, made predominantly by amacrine cells, and ribbon synapses, formed by photoreceptor and bipolar cells. To identify molecular differences between these synapse types, we have compared the distribution of the synapsins, a family of nerve terminal phosphoproteins, with that of synaptophysin (p38) and SV2, two intrinsic membrane proteins of synaptic vesicles. We report an absence of synapsin I and II immunoreactivity from all ribbon-containing nerve terminals. These include terminals of rod cells in developing and adult rat retina, rod and cone cells in monkey and salamander retinas, and rat bipolar cells. Furthermore, we show that synapsins I and II are differentially distributed among conventional synapses of amacrine cells. The absence of the synapsins from ribbon synapses suggests that vesicle clustering and mobilization in these terminals differ from that in conventional synapses.     

Modelling and simulation of vertebrate retina

In the present work we investigate the neuronal activities in a vertebrate retina by modelling and simulations using the results of (Oguztöreli, 1979). The basic retinal network considered here consists of interconnected five neurons: a receptor cell (rod or cone), a horizontal cell, a bipolar cell, an amacrine cell, and a retinal ganglion cell. The mathematical model for the basic network is a system of nonlinear ordinary integral differential difference equations. A number of simulations describing the dynamics of the neural activities in the basic network under different conditions are presented, actual and steady-state solutions are discussed. An algorithm is proposed for the determination of the system parameters experimentally.This work was supported by the Natural Sciences and Engineering Research Council Canada under Grant NSERCA-4345 through the University of Alberta