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Biomedical subjects

K Cusato

Publications and source records attributed to K Cusato.

7 recordsLinked to original sources
PubMed2006

Hypoglycemia leads to age-related loss of vision.

The retina is among the most metabolically active tissues in the body, requiring a constant supply of blood glucose to sustain function. We assessed the impact of low blood glucose on the vision of C57BL/6J mice rendered hypoglycemic by a null mutation of the glucagon receptor gene, Gcgr. Metabolic stress from moderate hypoglycemia led to late-onset loss of retinal function in Gcgr(-/-) mice, loss of visual acuity, and eventual death of retinal cells. Retinal function measured by the electroretinogram b-wave threshold declined >100-fold from age 9 to 13 months, whereas decreases in photoreceptor function measured by the ERG a-wave were delayed by 3 months. At 10 months of age Gcgr(-/-) mice began to lose visual acuity and exhibit changes in retinal anatomy, including an increase in cell death that was initially more pronounced in the inner retina. Decreases in retinal function and visual acuity correlated directly with the degree of hypoglycemia. This work demonstrates a metabolic-stress-induced loss of vision in mammals, which has not been described previously. Linkage between low blood glucose and loss of vision in mice may highlight the importance for glycemic control in diabetics and retinal diseases related to metabolic stress as macular degeneration.

Age Factors↗
PubMed2006

Gap junctions remain open during cytochrome c-induced cell death: relationship of conductance to 'bystander' cell killing.

Previous reports have shown that gap junctions relay cell death in many cell types. However, changes in electrical coupling and their dynamics during cell death are poorly understood. We performed comprehensive studies of electrical coupling following induction of cell death by single-cell cytochrome c (cyC) injection in paired Xenopus oocytes. Cell death was rapidly induced by cyC in injected cells, and cell death was also observed in uninjected bystander cells electrically coupled to the cyC-injected oocytes. Gap junction currents either remained at pre-cyC injection levels or increased dramatically as the injected cell died. Nonjunctional currents increased in injected cells immediately following cyC injection; nonjunctional currents increased slowly in uninjected bystander cells. Bystander cell death occurred only when junctional conductance was approximately 6 muS. Both 1,2-bis-(o-aminophenoxy)-ethane-N,N,-N',N'-tetraacetic acid tetraacetoxy-methyl ester and Xestospongin C inhibited bystander cell death in pairs that had reached the death conductance threshold, suggesting that Ca(2+) and inositol 1,4,5 triphosphate are involved in the process.

Animals↗
PubMed2001

Two phases of increased cell death in the inner retina following early elimination of the ganglion cell population.

Neurons in the inner nuclear layer (INL) of the vertebrate retina undergo considerable programmed cell death during development, but the determinants of this cell death remain largely unknown. The present study examines the role of retinal ganglion cells in support of INL neurons in the developing ferret retina. The retinal ganglion cell population was eliminated by optic nerve transection at postnatal day (P) 2, and the incidence of cell death was examined using terminal deoxytransferase dUTP nick-end labelling (TUNEL) at various ages during the first 3 postnatal weeks. Significant increases in TUNEL-positive cells were observed in the neuroblast layer (NBL) as early as P3, prior to synapse formation within the inner plexiform layer (IPL), and again in the INL at P22, the normal peak of naturally occurring cell death within the ferret's INL. A decrease in TUNEL-positive cells was found in the NBL at P8. These results show three phases of response to the loss of retinal ganglion cells and suggest that cells in the NBL/INL are normally dependent on retinal ganglion cells for their survival. Recent studies have shown that certain populations of retinal neurons are reduced in adult animals that had lost the population of ganglion cells during early development, so the present study also examined when this reduction could first be detected. The number of parvalbumin-immunoreactive amacrine cells was decreased significantly in the NBL of the manipulated eye as early as P8, when we could first label this population, and this difference persisted through adulthood. The fact that cell death in the NBL has already increased within 24 hours of ganglion cell elimination, coupled with the specificity of this effect on the adult complement of INL cell types, shows that cell-cell interactions controlling survival are already highly specific for particular types of retinal neuron early in development

Animals↗
PubMed1999

Rods and cones project to the inner plexiform layer during development.

Mature rod and cone photoreceptor cells extend terminals to the outer plexiform layer (OPL), where they form characteristic spherules or pedicles, synapsing with the second-order neurons of the inner nuclear layer (INL). The present study demonstrates that, prior to the formation of this connectivity, immature rods and cones in the ferret extend processes beyond the level of the horizontal cells and future OPL, reaching the inner plexiform layer (IPL). The number of processes extending to the IPL increases steadily as the population of photoreceptor cells expands postnatally, reaching a maximum 2 weeks after birth. These processes are immunopositive for synaptophysin, and they terminate in two strata occupied by the dendrites of amacrine cells and ganglion cells. The frequency of these processes declines rapidly during the third postnatal week, and they are no longer detectable by the fourth postnatal week. Their loss is neither a consequence of photoreceptor cell death nor is it due to selective protein trafficking mechanisms that render them immunonegative. Rather, these processes retract to the level of the OPL during this period, coincident with the maturation of bipolar and horizontal cell processes. These results demonstrate that, despite the clear presence of environmental signals presaging the formation of the OPL, photoreceptor terminals initially ignore them to grow beyond this level of the retina. Rather, they detect and respond to signals within the IPL during this period, terminating in proximity to the processes of other cells in the inner retina, where they may contribute to transient retinal circuitry during early development.

Animals↗
PubMedDate not supplied

Organization of the inner retina following early elimination of the retinal ganglion cell population: effects on cell numbers and stratification patterns.

The present study has examined the effects of early ganglion cell elimination upon the organization of the inner retina in the ferret. The population of retinal ganglion cells was removed by optic nerve transection on the second postnatal day, and retinas were subsequently studied in adulthood. Numbers of amacrine and bipolar cells were compared in the nerve-transected and nerve-intact retinas of operated ferrets, while stratification patterns within the inner plexiform layer were compared in these and in normal ferret retinas. Early ganglion cell elimination was found to produce a 25% reduction in the population of glycine transporter-immunoreactive amacrine cells, and 18 and 15% reductions in the populations of parvalbumin and calbindin-immunoreactive amacrine cells, respectively. GABAergic amacrine cells were also reduced by 34%. The number of calbindin-immunoreactive displaced amacrine cells, by contrast, had increased in the ganglion cell-depleted retina, being three times their normal number. Other amacrine and bipolar cell types were unaffected. Despite these changes, the stratification patterns associated with these cell types remained largely intact within the inner plexiform layer. The present results demonstrate a class-specific dependency of inner retinal neurons upon the ganglion cell population in early postnatal life, but the ganglion cells do not appear to provide any critical signals for stratification within the inner plexiform layer, at least not after birth. Since they themselves do not produce stratified dendritic arbors until well after birth, the signals for stratification of the bipolar and amacrine cell processes should arise from other sources.

Amino Acid Transport Systems, Neutral↗