PubMed Health⌕ Search

Biomedical subjects

M Devadas

Publications and source records attributed to M Devadas.

12 recordsLinked to original sources
PubMed2006

Dopaminergic agents affect the ability of brief periods of normal vision to prevent form-deprivation myopia.

Placing a translucent diffuser over the eye of a chick causes the eye to grow excessively, resulting in form-deprivation myopia. For chickens kept on a 12:12 h light/dark cycle, removing the diffuser for 3 h during the light period protects against the excessive growth, but if the bird is kept in the dark for this 3-h period, the protective effect is abolished. Injecting dopamine agonists into the eye during this 3-h dark period restores the protective effect, which can be blocked by dopamine antagonists injected just prior to diffuser removal in the light. These responses are mediated by D2 receptors, suggesting that the protective effect of normal vision against form-deprivation is mediated through the stimulation of dopamine release and activation of D2-dopamine receptors.

Animals↗
PubMed2002

Na,K-ATPase alpha3 subunit in the goldfish retina during optic nerve regeneration.

The goldfish optic nerve can regenerate after injury. To understand the molecular mechanism of optic nerve regrowth, we identified genes whose expression is specifically up-regulated during the early stage of optic nerve regeneration. A cDNA library constructed from goldfish retina 5 days after transection was screened by differential hybridization with cDNA probes derived from axotomized or normal retina. Of six cDNA clones isolated, one clone was identified as the Na,K-ATPase catalytic subunit alpha3 isoform by high- sequence homology. In northern hybridization, the expression level of the mRNA was significantly increased at 2 days and peaked at 5-10 days, and then gradually decreased and returned to control level by 45 days after optic nerve transection. Both in situ hybridization and immunohistochemical staining have revealed the location of this transient retinal change after optic nerve transection. The increased expression was observed only in the ganglion cell layer and optic nerve fiber layer at 5-20 days after optic nerve transection. In an explant culture system, neurite outgrowth from the retina 7 days after optic nerve transection was spontaneously promoted. A low concentration of ouabain (50-100 nm ) completely blocked the spontaneous neurite outgrowth from the lesioned retina. Together, these data indicate that up-regulation of the Na,K-ATPase alpha3 subunit is involved in the regrowth of ganglion cell axons after axotomy.

Amino Acid Sequence↗
PubMed2001

Changes in NADPH diaphorase expression in the fish visual system during optic nerve regeneration and retinal development.

The various functions of nitric oxide (NO) in the nervous system are not fully understood, including its role in neuronal regeneration. The goldfish can regenerate its optic nerve after transection, making it a useful model for studying central nervous regeneration in response to injury. Therefore, we have studied the pattern of NO expression in the retina and optic tectum after optic nerve transection, using NADPH diaphorase histochemistry. NO synthesis was transiently up-regulated in the ganglion cell bodies, peaking during the period when retinal axons reach the tectum, between 20-45 days after optic nerve transection. Enzyme activity in the tectum was transiently down-regulated and then returned to control levels at 60 days after optic nerve transection, during synaptic refinement. To compare NO expression in the developing and regenerating retina, we have looked at NO expression in the developing zebrafish retina. In the developing zebrafish retina the pattern of staining roughly followed the pattern of development with the inner plexiform layer and horizontal cells having the strongest pattern of staining. These results suggest that NO may be involved in the survival of ganglion cells in the regenerating retina, and that it plays a different role in the developing retina. In the tectum, NO may be involved in synaptic refinement.

Animals↗
PubMed2001

Reactive oxygen species uncouple external horizontal cells in the carp retina and glutathione couples them again.

We have investigated the effect of free radicals on the electrical gap junctions between horizontal cells in the carp retina. In our previous study, L-buthionine sulfoximine, an inhibitor of glutathione synthesis, caused uncoupling of horizontal cells four days after injection. In the present study, we have used paraquat, a generator of exogenous reactive oxygen species, to investigate whether it was the depletion of glutathione or an increase in the level of reactive oxygen species which resulted in horizontal cell uncoupling after L-buthionine sulfoximine injection. Intracellular recordings were made from L-type horizontal cells at various time-points after intravitreal injection of paraquat. Injection of 25nmol paraquat caused an increase in response amplitude to central spot light stimuli by two days after injection, which continued for a further two to three days and had almost disappeared by seven days after injection. There was also a sharp increase in reactive oxygen species production, peaking at four days and disappearing by seven days after injection, and an accompanying depletion and a restoration of glutathione levels with a similar time-course. Marking cells with Lucifer Yellow clearly illustrated uncoupling of horizontal cells after paraquat injection. If paraquat and L-buthionine sulfoximine were injected simultaneously, the increase in response to central spots was observed as early as one day after injection. This response amplitude was not more enhanced than that observed after L-buthionine sulfoximine injection alone, although a dramatic increase in the level of reactive oxygen species was observed. From these results, we suggest that reactive oxygen species are involved in uncoupling, while recovery from uncoupling is dependent on glutathione. Furthermore, we conclude that a balance between glutathione and reactive oxygen species levels is the most important factor controlling gap junctional intercellular communication of L-type horizontal cells in the carp retina.

Animals↗
PubMed2000

Slow recovery of goldfish retinal ganglion cells' soma size during regeneration.

The goldfish optic nerve regenerates after sectioning. Recently both short-term (30 days) and long-term (4 months) recovery of various goldfish behaviors were observed after optic nerve section. Using intracellular injection of Lucifer Yellow (LY) the morphology of regenerating ganglion cells in goldfish retina after optic nerve section over a 4 month period have been investigated. In normal retinas, most cells (96-98%) were 7-10 microm in soma diameter which increased with increasing distance from the optic disc. Only two or three short, thin processes could be traced with LY. The remaining cells (2-4%) were 13-16 microm in soma diameter and all of the long dendritic trees could be traced with LY. The most conspicuous morphological change observed was cellular hypertrophy, which occurred for 20-90 days after axotomy. Neuronal processes were also hypertrophic in this period. The percentage increase in hypertrophy of the central ganglion cells tended to be slightly higher compared to cells from other regions. These morphological changes peaked at 60 days after axotomy and fully disappeared by 120 days after axotomy. The slow recovery of ganglion cells' soma size may reflect the slow return to the normal number of optic axon terminals in the tectum during regeneration.

Animals↗
PubMed1999

Glutathione depletion causes an uncoupling effect on retinal horizontal cells through oxidative stress.

To investigate a physiological role of glutathione in the horizontal cells of carp retina, the gap junctional intercellular communication between horizontal cells was studied using the techniques of intracellular recording of light-induced responses and coupling of the fluorescence dye Lucifer Yellow. Intravitreal injection of 2.5 micromol L-buthionine sulfoximine, an inhibitor of glutathione synthesis, induced a dramatic reduction (20% of control) of retinal glutathione level two days after treatment. The low level of glutathione continued for a further four to five days, and thereafter gradually recovered to about 40% (20 days after injection) and 70% (50 days after injection) of the control level. The spatial properties of the photopic L-type horizontal cell response were examined by enlarging the diameter of the central spot and peripheral annulus over the recording point. In normal retinas, the response amplitude of horizontal cells was monotonically enhanced as the diameter of the spot increased (0.5-4.0 mm) and correspondingly the dye diffusion area was wide, as the injected Lucifer Yellow normally diffused to several neighboring cells. Treatment with L-buthionine sulfoximine significantly altered the spatial properties of horizontal cells by increasing the response amplitude to central spots and slightly decreasing that to peripheral annuli, which were observed by four days after injection. It also restricted intracellular Lucifer Yellow to one or two cells. Accompanying the recovery of the cellular level of glutathione, the spatial properties and dye coupling of horizontal cells were restored to normal. A time lag (two days) of initiation in retinal glutathione depletion and alteration of spatial or dye coupling properties of horizontal cells is discussed, together with reactive oxygen species accumulation.

Animals↗
PubMed1999

Fast and slow recovery phases of goldfish behavior after transection of the optic nerve revealed by a computer image processing system.

As the goldfish is a common experimental animal for vision research, including psychophysical behavior, it is very important to quantitatively score fish behavior. We have previously developed a computer image processing system which can acquire the positional coordinates of goldfish moving freely in an aquarium and determine turning directions (go straight, right or left turn). In the present study, an algorithm to determine tilting angles of moving goldfish was constructed. We also made histograms for quantifying the interaction between pairs of goldfish (two-point distance). By using these histograms, we estimated the time-course of behavioral regeneration after optic nerve transection in goldfish. Control goldfish showed an equal percentage of right or left turns and maintained an upright position in a dorsoventral axis. When the optic nerve of a goldfish was unilaterally sectioned, the goldfish showed predominant turning and slight tilting toward the intact eye. The abnormal turning and tilting behaviors lasted for 10-14 days and then gradually decreased, returning to control behaviors by one month after the unilateral transection. When the optic nerve of a single goldfish was bilaterally sectioned, it did not show any preferential turning and tilting behavior, which is similar to what was observed in control goldfish. However, the trace maps showed that, after bilateral sectioning, fish preferred to cross the center of the tank, which was unlike control fish. In control pairs, one goldfish chased the other with a fixed small range of two-point distances. However, in pairs of goldfish with bilateral transection of the optic nerve, the blind goldfish behaved independently of each other, with a long two-point distance. The long two-point distance of the blind goldfish lasted for at least two months and then slowly returned to control two-point distance by four months after bilateral transection. Such fast and slow recovery in goldfish behaviors evoked after unilateral and bilateral transection of the optic nerve is discussed with respect to reconnection of regenerating optic nerves in the fish central nervous system. This computer image processing system is a useful tool with which we can quickly and easily quantify fish behavior.

Algorithms↗
PubMed1997

Retinal control of scleral precursor synthesis.

There is a light-dependent diurnal rhythm in scleral precursor synthesis (SPS). In form-deprivation myopia (FDM) there is an increase in SPS. Daily periods of normal vision prevent FDM, but light intensities that maintain the retinal dark-light switch in its dark state do not, implicating melatonin, dopamine, enkephalin, neurotensin and somatostatin in the control of SPS. FDM is also prevented by pirenzepine, a cholinergic muscarinic antagonist To test if these compounds control the rate of SPS, agonists and antagonists were applied directly to the sclera, but the only effects detected were at very high concentrations, making them physiologically insignificant.

Adaptation, Ocular↗
PubMed1996

Light controls scleral precursor synthesis.

Both axial clongation and scleral precursor synthesis are increased during form deprivation myopia (FDM). Since axial clongation is greater during the day than at night during normal development, it seemed likely that the rate of scleral precursor synthesis would be high in the day and low at night. Instead we found that the rate of scleral precursor synthesis is greater in the middle of the night than at the middle of the day. The rise and fall do not begin until about 4 h after lights off or lights on, respectively. These variations in precursor synthesis are light-driven, not circadian.

Animals↗