Signals relayed through the magnocellular layers of the LGN travel on axons with faster conduction speeds than those relayed through the parvocellular layers. As a result, magnocellular signals might reach cerebral cortex appreciably before parvocellular signals. The relative speed of these two channels cannot be accurately predicted based solely on axon conduction speeds, however. Other factors, such as different degrees of convergence in the magnocellular and parvocellular channels and the retinal circuits that feed them, can affect the time it takes for magnocellular and parvocellular signals to activate cortical neurons. We have investigated the relative timing of visual responses mediated by the magnocellular and parvocellular channels. We recorded individually from 78 magnocellular and 80 parvocellular neurons in the LGN of two anesthetized monkeys. Visual response latencies were measured for small spots of light of various intensities. Over a wide range of stimulus intensities the fastest magnocellular response latencies preceded the fastest parvocellular response latencies by about 10 ms. Because parvocellular neurons are far more numerous than magnocellular neurons, convergence in cortex could reduce the magnocellular advantage by allowing parvocellular signals to generate detectable responses sooner than expected based on the responses of individual parvocellular neurons. An analysis based on a simple model using neurophysiological data collected from the LGN shows that convergence in cortex could eliminate or reverse the magnocellular advantage. This observation calls into question inferences that have been made about ordinal relationships of neurons based on timing of responses.

Electrophysiologically, color-opponent retinal bipolar cells respond with opposite polarities to stimulation with different wavelengths of light. The origin of these different polarities in the same bipolar cell has always been a mystery. Here we show that an intracellularly recorded and HRP-injected, red-ON, blue/green-OFF bipolar cell of the turtle retina made invaginating (ribbon associated) synapses exclusively with L-cones. Non-invaginating synapses resembling wide-cleft basal junctions were made exclusively with M-cones. Input from S-cones was not seen. From these results we suggest sign-inverting transmission from L-cones at invaginating synapses via metabotropic glutamate receptors, and sign-conserving transmission from M-cones at wide-cleft basal junctions via ionotropic receptors. To explain the pronounced blue sensitivity of the bipolar cell, computer simulations were performed using a sign-conserving input from a yellow/blue chromaticity-type (H3) horizontal cell. The response properties of the red-ON, blue/green-OFF bipolar cell could be quantitatively reproduced by this means. The simulation also explained the asymmetry in L- and M-cone inputs to the bipolar cell as found in the ultrastructural analysis and assigned a putative role to H3 horizontal cells in color processing in the turtle retina.

This study used the swept spatial-frequency method to compare retinal and cortical acuity in anesthetized young adult rhesus monkeys. Visual evoked potentials (VEPs) and pattern electroretinographic responses (PERGs) were recorded from 25 monkeys (age range: 4–12 years) anesthetized with a continuous infusion of propofol. The stimuli were temporally countermodulated sine-wave gratings that increased in spatial frequency within a 10.24-s period. All animals were refracted using acuity estimated from the zero micro-volt intercept of the linear regression of evoked potential amplitude on spatial frequency. Average sweep acuities were 23.7 cycles/deg ± 1.5 S.E.M. and 23.1 cycles/deg ± 1.8 S.E.M. for the PERG and VEP, respectively. VEP and PERG acuities were within the range expected based on acuities estimated from behavioral studies in macaques. PERG and VEP acuities were highly correlated (r = 0.90) and equally sensitive to spherical blur. On a subset of animals, test–retest reliability of animals, and interocular correlations, were high (r = 0.87 and r = 0.83, respectively). Increasing propofol dosage 8-fold did not degrade PERG or VEP acuity. This study demonstrates that high spatial-frequency acuities can be rapidly obtained from young adult rhesus monkeys under a wide dose range of propofol anesthesia using the swept spatial-frequency method.

Nitric oxide (NO) is a novel neuronal messenger that likely influences retinal function by activating retinal guanylyl cyclase to increase levels of cGMP. In the present study, the localization of neuronal nitric oxide synthase (nNOS, Type I NOS) in the cone-dominant tree shrew retina was studied using NADPH-d histochemistry and nNOS immunocytochemistry. Both NADPH-d and nNOS-immunoreactivity (IR) labeled the inner segments of rods and the myoids of a regular subpopulation of cones, with their corresponding nuclei outlined. The labeled cone myoids were co-localized with a marker for short-wave-sensitive (SWS) cones (S-antigen) and also displayed the regular triangular packing and density (7%) characteristic of SWS cones in tree shrew and other mammalian retinas. These measures confirmed the identity of the labeled cones as SWS cones. Photoreceptor ellipsoids of all cones were strongly labeled by NADPH-d reactivity, but lacked nNOS-IR. Another novel finding in tree shrew retina was that both NADPH-d and nNOS-IR labeled Müller cells, which have not been labeled by nNOS-IR in other mammalian retinas. Consistent with findings in rod-dominant retinas, two types of amacrine cells at the vitreal edge of the inner nuclear layer and a subpopulation of displaced amacrine cells at the scleral edge of the ganglion cell layer were labeled by both NADPH-d and nNOS-IR. Processes of these labeled cells were seen to extend into the inner plexiform layer, where dense punctate label was seen, especially in the central sublamina. These results show that localization of NOS in the cone-dominant tree shrew retina shares some common properties with rod-dominant mammalian retinas, but also shows some species-specific characteristics. The new finding of nNOS localization in tree shrew SWS cones and rods, but not in other cones, raises interesting questions about the roles of NO in the earliest level of visual processing.

Calretinin-containing retinal amacrine cells are heterogeneous with regard to their neurochemical properties. In the rabbit retina, about 90% of them contain glycine, as evidenced in the present study by double-label immunocytochemistry. In a previous report, we showed that a small population of amacrine cells contains both γ-aminobutyric acid and calretinin. In this study, we further identified this cell population by means of known secondary markers. However, none of the markers we tested (choline acetyltransferase, serotonin accumulation, NADPH-diaphorase, vasoactive intestinal polypeptide) co-localized with calretinin. A small population (1%) of the cells in the ganglion cell layer contains both calretinin and glycine. Since calretinin-positive cells in the ganglion cell layer have been identified as ganglion cells based on soma size and presence of calretinin-positive axons in the optic nerve fiber layer, this population may represent a class of ganglion cell which contains glycine. Our results, together with those of other studies, suggest that calretinin is not a general marker of any of the well-known amacrine cell types in the mammalian retina. Rather, calretinin, just as other calcium-binding proteins, is distributed in a species-specific manner. At the same time it appears that, as shown for horizontal cells, one or more of the major buffer-type calcium-binding proteins of the EF-hand family is present in most of the retinal amacrine cells.

To study processing of UV stimuli in the retina of the turtle, Trachemys dorbignii, we recorded intracellular responses to spectral light from 89 cells: 54 horizontal (47 monophasic, five (R/G) biphasic and two (Y/B) triphasic), 14 bipolar, 12 amacrine, and nine ganglion cells. Spectral sensitivities were measured with monochromatic flashes or with the dynamic constant response method in dark or chromatic adapted states. Stray light and second-order harmonics were also measured. (1) All cells responded to UV stimuli, although none had maximum sensitivity in the UV. (2) Most horizontal, bipolar, and amacrine cells had red-peaked spectral sensitivities. (3) Red adaptation of all monophasic horizontal cells indicated a single red input, except one that had additional peaks in the blue and UV. (4) Responses of biphasic and triphasic horizontal cells to UV light were always hyperpolarizing. Opposition between hyperpolarizing and depolarizing responses at long wavelengths indicates that UV responses were not due to the beta band of red receptors. (5) An unstained spectrally opponent bipolar cell hyperpolarized in the center to green light and antagonistically depolarized in the surround to UV, blue, and green flashes, but hyperpolarized to red. (6) All dark-adapted amacrine cells were red-peaked monophasic cells, but red adaptation broadened their spectral-sensitivity curves or displaced their peaks. An A15, an A18, and an A24 wide-field amacrine cell were stained. (7) A G15 bistratified ganglion cell is shown here for the first time to be spectrally opponent. This UVB/RG cell depolarized to UV and blue and hyperpolarized to red and green. It differs from previously reported turtle ganglion cells in being color opponent in the entire field, not only in the surround, and in showing spatial opponency.

A nonlinear interaction between signals from at least two spatially displaced receptors is a fundamental requirement for a direction-selective motion detector. This paper characterizes the nonlinear mechanism present in the motion detector pathway that provides the input to wide-field directional neurons in the nucleus of the optic tract of the wallaby, Macropus eugenii. An apparent motion stimulus is used to reveal the interactions that occur between adjacent regions of the receptive fields of the neurons. The interaction between neighboring areas of the field is a nonlinear facilitation that is accurately predicted by the outputs of an array of correlation-based motion detectors (Reichardt detectors). Based on the similarity between the output properties of the detector array and the real neurons, it is proposed that the interaction between neighboring regions of the receptive field is a second-order nonlinearity such as a multiplication. The results presented here for wallaby neurons are compared to data collected from directional systems in other species.

To assess the contribution of spiking inner retinal neurons to the multifocal electroretinogram (ERG), recordings were made from four monkeys (Macaca mulatta) before and after intravitreal injections of tetrodotoxin (TTX). TTX blocks all sodium-based action potentials and thus terminates spiking activity of amacrine and ganglion cells. TTX eliminated a large component from the control responses, and this TTX-sensitive component was present as early as 10 ms after the stimulus. Before injection with TTX, the 103 focal ERG responses varied in waveform across the retina. After TTX, the response waveforms were largely independent of retinal position, indicating that it was primarily the TTX-sensitive component of the control response that was dependent upon retinal location. Given that retinal ganglion cells compose a sizable proportion of the retinal elements that produce action potentials, it is likely that part of the TTX-sensitive component is due to the spiking activity of these cells. Further, the systematic change in waveform of the TTX-sensitive component with distance from the optic nerve head suggests that part of the TTX-sensitive component may originate from the activity of the ganglion cell axons. Based on these findings, there is reason to be optimistic that the multifocal technique can be employed to study the effects of glaucoma and other diseases that affect the inner retina.

Previous studies in the rabbit retina have shown that drugs which block AMPA glutamate receptors abolish directional selectivity in ON–OFF directionally selective (DS) ganglion cells. The effects of activation of AMPA receptors on the directionally selective responses of these ganglion cells had not been studied. In the present study, extracellular recordings of the responses of ON–OFF DS ganglion cells to a moving bar of light were made in an in vitro rabbit retinal preparation. In control solution, bath application of AMPA (7–10 μM) abolished the light responses of most ON–OFF DS ganglion cells. On washout of AMPA, the light responses rapidly returned; however, the cells temporarily lost the ability to discriminate the direction of the moving bar of light. That is, the cells responded equally to movement in the preferred and null directions. Pretreatment of retinas with the glycine receptor antagonist strychnine (1–2 μM) did not alter the effects of AMPA. On the other hand, in retinas pretreated with the GABAA receptor antagonist SR95531 (0.2–0.25 μM), AMPA did not abolish the light responses of ON–OFF DS ganglion cells but instead abolished directional selectivity in these cells by bringing out a response to movement in the null direction. This finding suggests that an AMPA-induced GABA efflux from cells in the retina was responsible for the suppression of the light responses by AMPA. In control solution, application of the selective AMPA receptor agonist (S)-5-fluorowillardiine (2–3 μM) only temporarily abolished the light responses of ON–OFF DS ganglion cells. As the light responses returned, it was clear that directional selectivity had been abolished by (S)-5-fluorowillardiine. In control solution, blocking AMPA receptor desensitization with cyclothiazide (80–100 μM) greatly reduced the light responses of ON–OFF DS ganglion cells. As the light responses slowly returned on washout of cyclothiazide, directional selectivity was clearly reduced although not abolished. In retinas pretreated with SR95531, application of cyclothiazide abolished directional selectivity. Diazoxide (700–1000 μM), another blocker of AMPA receptor desensitization, abolished directional selectivity in ON–OFF DS ganglion cells without the need of adding SR95531 to the bathing solution. It is concluded that, in the rabbit retina, AMPA receptors play an important role in generating directional selectivity in ON–OFF DS ganglion cells. Moreover, excessive activation of AMPA receptors greatly compromises the mechanism for directional selectivity in ON–OFF DS ganglion cells.

Form deprivation has been shown to result in myopia in a number of species such that the eye enlarges if one eye is permanently closed at the time of eye opening. In the quokka wallaby, the eye grows slowly throughout life. After form deprivation, the eye enlarges by 1–1.5 years of age to the size of that in a 4–6-year-old animal and the number of multinucleated retinal pigment epithelial (RPE) cells in the enlarged retina remains much lower than would be expected in eyes of comparable size. Here we have repeated the experiment but examined animals at 4 years of age. The sutured eye grew significantly larger than did its partner. Numbers of RPE cells were comparable between sutured and partner eyes but were lower than in normal animals of similar age. Reductions in RPE cell density were greater in nasal than in dorsal or ventral retina and were not seen in temporal retina. The distribution of multinucleated cells was quite different in the sutured and open eyes. As in normal eyes, partner eyes had most multinucleated cells in ventral retina, while in the sutured eyes such cells were located mainly in the far periphery. In conclusion, the RPE is significantly changed by the eye enlargement process. However, it is not known whether this change results from an active part played by the RPE in the retinal expansion process or whether the changes are simply a result of a passive increase in area of the RPE.

We studied the effects of contextual modulation in area V1 of anesthetized macaque monkeys. In 146 cells, responses to a single line over the center of the receptive field were compared with those to full texture patterns in which the center line was surrounded by similar lines at either the same orientation (uniform texture) or the orthogonal orientation (orientation contrast). On average, the responses to single lines were reduced by 42% when texture was presented in the surround. Uniform textures often produced stronger suppression (7% more, on average) so that lines with orientation contrast on average evoked larger responses than lines in uniform texture fields. This difference is correlated with perceptual differences between such stimuli, suggesting that physiological mechanisms contributing to the saliency (“popout”) of textural stimuli operate, at least to some degree, even under anesthesia. Significant response modulation by the texture surround was seen in 112 cells (77%). Fifty-three cells (36%) responded differently to the two texture patterns; response preferences for orientation contrast (35 cells; 24%) were seen more often than preferences for uniform textures (18 cells; 12%). The remaining 59 cells (40%) were similarly suppressed by both texture surrounds. Detailed analysis of texture modulation revealed two major components of surround effects: (1) fast nonspecific (“general”) suppression that occurred at about the same latency as excitatory responses and was found in all layers of striate cortex; and (2) differential response modulation that began about 60–70 ms after stimulus onset (about 15–20 ms after the onset of the excitatory response) and was less homogeneously distributed over cortical layers.

Electrical coupling between H2 horizontal cell pairs isolated from the hybrid bass retina was studied using dual whole-cell, voltage-clamp technique. Voltage-dependent inactivation of junctional currents in response to steps in transjunctional voltage (Vj) over a range of ±100 mV was characterized for 89 cell pairs. Approximately one-quarter of the pairs exhibited strongly voltage-dependent junctions (>50% reduction in junctional current at ±100 mV), another quarter of the pairs exhibited voltage-independent junctional current (<5% reduction at ±100 mV), and the remainder of the pairs exhibited intermediate values for voltage inactivation. We focused on further characterizing the Vj-independent junctions of horizontal cells, which have not been described previously in detail. When Lucifer Yellow dye was included in one recording pipette, pairs exhibiting Vj-independent coupling showed no (9/12), or limited (3/12), passage of dye. Vj-independent coupling was markedly less sensitive to the modulators SNP (100–300 μM, −9% reduction in coupling) and dopamine (100–300 μM, −6%) than were Vj-dependent junctions (−45% and −44%). However, simultaneous application of both SNP and dopamine significantly reduced Vj-independent coupling (−56%). Both Vj-independent and Vj-dependent junctions were blocked by DMSO (1–2%), but Vj-independent junctions were not blocked by heptanol. Single-channel junctional conductances of Vj-independent junctions range from 112–180 pS, versus 50–60 pS for Vj-dependent junctions. The results reveal that Vj-independent coupling in a subpopulation of horizontal cells from the hybrid bass retina is mediated by cellular junctions with physiological and pharmacological characteristics distinct from those previously described in fish horizontal cells.

The zebrafish has recently assumed a central position in the study of vertebrate development. Numerous studies of other fish have shown that their central nervous systems, and especially their visual systems, continue to add new neurons throughout life, which is probably related to their abilities to regenerate axons and whole nervous tissue. Retinal neurogenesis had not been examined in adult zebrafish, and two reports concluded that the optic tectum ceased neurogenesis early in life, so the question arose whether the zebrafish was anomalous in this regard. We labeled embryonic (24- and 48-h postfertilization) and adult zebrafish with the thymidine analog, bromo-deoxyuridine, and, after short and long survivals, examined the retina and brain for labeled cells. They were abundant in both the optic tectum and the retina. Although the rate of retinal growth slows considerably between embryonic and adult stages, the patterns of neurogenesis in both the embryo and the adult are similar to those described in other fish, so these “fish-specific” features of general interest can justifiably be studied in zebrafish.

We have studied the postnatal development of presumptive axon terminals (puncta) which were recognized by antibodies to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and were located on the somata of area 17 neurons projecting to the ipsilateral area 18 of the visual cortex in cats ranging from 7 days of age to adulthood. Projection neurons were retrogradely labeled by injection of horseradish peroxidase conjugated to wheat germ agglutinin into the ipsilateral area 18. These neurons were mainly pyramidal in shape at all the developmental stages examined and the adult distribution of labeled cells was reached by 21 days. Subsequent GABA postembedding immunohistochemistry using high-resolution light microscopy was carried out to study the development of GABAergic terminals on cell bodies of identified projecting neurons in layers II–III. At all ages examined, we found perisomatic GABAergic puncta on these cells. Their density showed a significant increase from postnatal days 7 to 45, and then remained largely constant through adulthood. Since GABAergic puncta are considered the light-microscopic correlate of GABAergic synaptic terminals, our results support the idea of a developmentally regulated increase in the inhibitory activity of local interneurons on area 17 pyramidal neurons projecting to area 18 in the cat visual cortex which occurs within the same time frame as that of the acquisition of the mature operation of these cells.

Three 5-HT receptors have been implicated in retinal processing but positive identification of the receptors and the localization of receptor subtypes in the retina have not been achieved. In this study, molecular techniques were used to identify one class of 5-HT receptor—5-HT2a—in the retina, and immunohistochemical techniques were used to localize the receptor in the retinal network. Reverse transcription polymerase chain reaction (RT-PCR) techniques were used to identify a segment of the rabbit 5-HT2a gene; a 422 base fragment was identified, cloned, and sequenced. The fragment shows a high degree (ca. 90%) of nucleotide sequence identity with the 5-HT2a receptor gene from other mammals. 5-HT2a immunoreactivity was seen in both the inner and outer plexiform (synaptic) layers of the retina. Using cell-type-specific markers, the 5-HT2a immunoreactivity was shown to be on the terminals of photoreceptor and rod bipolar cells. This association of 5-HT2a receptors with these two synapses suggests that serotonin may be a modulator of synaptic function in the retina.

The avian ciliary ganglion (CG) controls choroidal blood flow by its choroidal neurons, and pupil constriction and accommodation by its ciliary neurons. It was previously reported that both choroidal and ciliary neurons label positively for NADPH diaphorase (NADPHd), a marker for nitric oxide synthase (NOS). To assess if this labeling is preganglionic or postganglionic and to determine if it is attributable to neuronal NOS (nNOS), we studied pigeon CG using NADPHd histochemistry and nNOS immunohistochemistry (IHC). Short-duration staining times by NADPHd histochemistry yielded intense labeling of structures that appeared to be the cap-like endings on ciliary neurons and the boutonal endings on choroidal neurons that arise from the nucleus of Edinger-Westphal (EW), and light or no postganglionic perikaryal staining. The light postganglionic staining that was observed tended to be localized to ciliary neurons. Consistent with this, NADPHd+ nerve fibers were observed in the postganglionic ciliary nerves but rarely in the postganglionic choroidal nerves. These same staining times yielded robust staining of neurons in the orbital pterygopalatine microganglia network, which are known to be nNOS+. Diffuse staining of CG perikarya was observed with longer staining durations, and this staining tended to mask the preganglionic labeling. Preganglionic NADPHd+ staining in CG with short staining times was blocked by the NOS inhibitors iodonium diphenyl (IDP) and dichlorophenol-indophenol (DPIP), but the diffuse postganglionic staining observed with the longer staining times was not completely blocked. Labeling of CG sections for substance P (SP) by IHC (which labels EW-originating preganglionic endings in CG) and subsequently for NADPHd confirmed that NADPHd was localized to preganglionic endings on CG neurons. Immunohistochemical double labeling for nNOS and SP or enkephalin further confirmed that nNOS is found in boutonal and cap-like endings in the CG. Two studies were then carried out to demonstrate that the nNOS+ preganglionic endings in CG arise from EW. First, NADPHd+ and nNOS+ neurons were observed in EW in pigeons treated with colchicine to enhance perikaryal labeling. Second, NADPHd+ and nNOS+ preganglionic endings were eliminated from CG ipsilateral to an EW lesion. These various results indicate that NOS is present in EW-arising preganglionic endings on choroidal and ciliary neurons in avian CG. NOS also appears to be found in some ciliary neurons, but its presence in choroidal neurons is currently uncertain.

In the visual system, nearby neurons of similar functional type have a tendency to fire synchronously. Cross-correlation analysis of spike discharges recorded from pairs of neurons has revealed that the synchronized activity is frequently associated with oscillatory firing patterns. However, the underlying neural mechanisms and functions of synchronization and oscillations are not well understood. In the present study, we simultaneously recorded spike discharges from multiple OFF-sustained type ganglion cells with no antagonistic surround (the dimming detectors) of the frog retina using a planar multi-electrode array and analyzed the temporal properties of light-evoked spike discharges. With full-field, temporally modulated diffuse illumination, cross-correlation analysis revealed the presence of the synchronous oscillatory pattern. The strength of the synchronized activity decreased slightly with increased intercellular distance. Synchronized spike discharges were detected even in cell pairs more than 2 mm apart. The frequency of oscillations peaked at approximately 30 Hz. The shuffled cross-correlogram was nearly flat, indicating that the synchronous oscillatory activities are most probably of neural origin. When GABAA antagonists were applied to the retina, oscillations were suppressed almost completely and the strength of the synchronized activity decreased with increased intercellular distance more sharply than control. When small spot illumination was applied to the overlapping receptive fields of an adjacent cell pair, a weak synchronized activity was evoked without accompanying oscillations. The same cell pair generated a strong synchronized activity accompanied with oscillations with full-field illumination. Our results suggest that local synchronous activities are generated via short-range neural interactions, and that the oscillatory activities are induced by long-range neural interactions and may contribute to the establishment of synchrony between widely separated neuronal populations.

In humans, an increasing density of foveal cone photoreceptors occurs slowly over several years after birth, and accounts for a region that subserves high visual acuity. Concurrently, inner retinal cells move centrifugally away from the foveal center. Such developmental rearrangements reflect complex cellular remodeling after the retinal neuronal cells have differentiated and have formed synapses. Explaining foveal morphogenesis is difficult, because differentiated neuronal cells seem incapable of moving actively. Presented here is a biomechanical explanation of how the above events occur. This hypothesis assumes that the cellular movements throughout the retinal layers occur passively as the eye grows and the retina is stretched. Retinal stretch was simulated using virtual engineering models that were analyzed with finite element analysis. A pit combined with retinal stretch causes the retinal layers to deform in a way that accounts for both the centrifugal and centripetal movement of various retinal cell types. Axially directed, tensile forces associated with stretching the retinal tissue surrounding the pit also accounts for the elongated morphology of foveal cone photoreceptors. These simulations suggest that a pit is required for both the centripetal displacement of cone cells toward the center of the fovea, and for the elongated foveal cone morphology. Since the primate fovea may have minimal impact on acuity, its primary role may be to initiate foveal morphogenesis in slowly developing eyes.

We have examined the distribution of the glycine transporter glyt-1 in retinae of macaques, cats, rabbits, rats, and chickens. In all species, all glycine-containing amacrine cells expressed immunoreactivity for glyt-1, though the intensity of immunoreactivity for glyt-1 did not appear to directly correlate with the intensity of immunoreactivity for glycine in individual cells. A small subpopulation of glycine-immunoreactive displaced amacrine cells or ganglion cells also expressed glyt-1 in retinae from macaques, cats, chickens, and rats but not in retinae from rabbits. In addition, in all species examined, some displaced amacrine cells also contained glycine but did not express glyt-1. In monkeys, cats, and rats, populations of cells which we interpret as being glycine-containing interplexiform cells expressed glyt-1; these cells lacked a content of glutamate, suggesting they are not bipolar cells. The glycine-containing bipolar cells did not express glyt-1, suggesting that these cells probably acquired their content of glycine by other means such as via gap junctional connections with glycine-containing amacrine cells.

The aim of the study was to determine whether memantine could slow down the changes seen in the rabbit and rat retina following ischemia/reperfusion. A “suction cup procedure,” which raises the intraocular pressure, was used to give an ischemic insult to the rabbit retina. The electroretinogram was recorded before ischemia and after 2 days of reperfusion. Memantine or saline (10 μl) was injected into the eye before ischemia. Immunohistochemistry was used to study the effect of ischemia/reperfusion on the GABA, ChAT, and αPKC immunoreactivities. Ischemia/reperfusion injury to the rat retina was induced by raising the intraocular pressure above the systolic blood pressure for 60 min, followed by reperfusion of 3–14 days. Memantine (5 mg/kg) or saline was injected i.p. at the onset of ischemia or reperfusion. Immunohistochemistry was used to study the effect of ischemia/reperfusion on the ChAT, αPKC, and Thy-1 immunoreactivities. In addition, morphometric analysis was carried out to determine the effects of ischemia/reperfusion on the thickness of the retina. Ischemia for 75 min caused a change in the nature of the normal GABA and ChAT immunoreactivities in the rabbit retina and a reduction in the b-wave of the electroretinogram. When memantine was injected into the vitreous humour at the onset of an ischemic insult, the changes in the GABA and ChAT immunoreactivities were reduced and the recovery of the reduced b-wave of the electroretinogram after 2 days reperfusion was enhanced significantly. Ischemia for 60 min followed by 3 days reperfusion showed a clear change in ChAT immunoreactivity in the rat retina. The Thy-1 immunoreactivity was only clearly altered after a reperfusion period of 7 days. Moreover, a measurable change in the thickness of the inner retinal layers was detected after 14 days of reperfusion. When given at the onset of ischemia, memantine counteracted the effect of ischemia/reperfusion to varying degrees. However, when memantine was given at the onset of the reperfusion this was not the case. The combined data show that a single injection of memantine given i.p. or intravitreally will protect the retina from a subsequent ischemic insult.