Electrical activity regulates dendritic reorganization in ganglion cells after neonatal retinal lesion in the cat

During the first month of postnatal life, the dendritic arborizations of cat retinal ganglion cells continue to develop and undergo a substantial remodeling. Mechanical and pharmacological interferences with the normal development induce, during this period of time, substantial modifications in ganglion cell morphology. Specifically, the degeneration of those neurons whose axons were severed by a neonatal retinal lesion leads to a zone depleted of ganglion cells. Neurons at the border of the depleted area develop an abnormal elongation of the dendritic trees toward the empty space. In the present paper, we report data showing that this dendritic reorganization can be prevented by blocking the electrical activity with repeated tetrodotoxin injections into the eye during the whole critical period. Our analysis was performed on neurons filled with horseradish peroxidase

Long-term treatment of the developing retina with the metabotropic glutamate agonist APB induces long-term changes in the stratification of retinal ganglion cell dendrites

The gradual restriction of initially multistratified retinal ganglion cell (RGC) dendrites into ON and OFF sublaminae of the inner plexiform layer (IPL) can be effectively blocked by treating the developing retina with 2-amino-4-phosphonobutyrate (APB), the metabotropic glutamate agonist, or by light deprivation. Previous studies have focused on the short-term consequences of such manipulations, so the long-term effects of arresting dendritic stratification on the structural development of RGCs are as yet unknown. In the present study, we have addressed this issue by performing a morphological analysis of alpha RGCs labeled by retrograde transport of horseradish peroxidase injected into the dorsal lateral geniculate nucleus of adult cats that received monocular injections of APB from postnatal (P) day 2 until P30. A large proportion of the alpha cells in the APB-treated eye (44%) were found to have multistratified dendrites that terminated in both the ON and OFF sublaminae of the IPL. The dendritic arborization pattern in the sublaminae of the IPL of these cells was asymmetric, showing a variety of forms. Immunolabeling of retinal cross-sections showed that mGLUR6 receptors appeared normal in density and location, while qualitative observation suggested an increase in the axonal arborization of rod bipolar cells. These findings indicate that long-term treatment of the neonatal retina with APB induces a long- lasting structural reorganization in retinal circuitry that most likely accounts for some of the previously described changes in the functional properties of RGCs

The impact of Basic Fibroblast Growth Factor on Photoreceptor function and morphology

To assess the impact of basic fibroblast growth factor (bFGF) on photoreceptor function and morphology. METHODS: Impact was assessed in two models. In one, the endogenous expression of bFGF in photoreceptors was raised by sectioning one optic nerve of rats 3 to 4 weeks before study. In the other, bFGF was injected into the vitreous chamber in rats and cats. Retinal function was assessed from the electroretinogram (ERG), and retinal morphology was studied using DNA dyes, immunolabeling, and in situ hybridization. RESULTS: In both models of bFGF upregulation, the ERG b-wave was suppressed over a wide stimulus range and in light- and dark-adapted conditions. The a-wave was not suppressed by either procedure and at the brightest intensities was enhanced by both procedures. In nerve-sectioned eyes, outer retina appeared normal histologically, but levels of bFGF protein in the inner and outer nuclear layers were raised, whereas bFGF mRNA levels remained unchanged. In both models, levels of synaptophysin in the outer plexiform layer and of cytochrome oxidase in inner segments were raised in association with increases in bFGF protein levels. CONCLUSIONS: bFGF increased the ability of photoreceptors to respond to light but attenuated the transmission of this response to inner retinal cells, presumably by blocking the photoreceptor-bipolar synapse. If the expression of bFGF protein is upregulated in human photoreceptor dystrophies, it may contribute a reversible component to the loss of vision. The relationship between these actions of bFGF and its ability to protect photoreceptors from stress remains to be established

Topical Treatment with Cord Blood Serum in Glaucoma Patients: A Preliminary Report

Purpose. To report data happened to be observed in two glaucoma patients treated with Cord Blood Serum (CBS) eyedrops. Design. Case report. Retrospective data analysis Methods. CBS topical eyedrops, characterized in advance for growth factors (GFs) content, were administered for two months with the aim to relieve their subjective symptoms, in two patients who had referred ocular surface discomfort, although in absence of any sign of keratopathy. As patients were also affected by advanced glaucoma at risk of vision loss, and under treatment with hypotensive drugs, they had been also monitored over the same period with IOP controls and Visual field tests in our Unit. Results. During subsequent visits, data from Mean Deviation and Pattern Standard Deviation in the Visual fields were retrospectively collected and compared before and after treatment with CBS, and an amelioration was observed. Conclusions. CBS contains a combination of GFs, which potentially exert a neuroprotective action and candidate CBS as an interesting natural source to be delivered in neurodegenerative ocular disorders. The incidentally observed amelioration in these two patients deserves further investigation in this respec

Coherent spin dynamics of an interwell excitonic gas in GaAs/AlGaAs coupled quantum wells

The spin dynamics of an interwell excitons gas has been investigated in n-i-n GaAs/AlGaAs coupled quantum wells (CQWs). In these heterostructures the electron and the hole are spatially separated in neighboring quantum wells by a narrow AlAs barrier, when an electric field is applied. The time evolution kinetics of the interwell exciton photoluminescence has been measured under resonant excitation of the 1sHH intrawell exciton, using a pulsed tunable laser. The formation of a collective exciton phase in time and the temperature dependence of its spin relaxation rate have been studied. The spin relaxation rate of the interwell excitons is strongly reduced in the collective phase. This observation provides evidence for the coherence of the indirect excitons collective phase at temperatures below a critical $T_c$.Comment: 8 pages, 9 figure

Saffron: A multitask neuroprotective agent for retinal degenerative diseases

Both age related macular degeneration (AMD) and light induced retinal damage share the common major role played by oxidative stress in the induction/progression of degenerative events. Light damaged (LD) rats have been widely used as a convenient model to gain insight into the mechanisms of degenerative disease, to enucleate relevant steps and to test neuroprotectants. Among them, saffron has been shown to ameliorate degenerative processes and to regulate many genes and protective pathways. Saffron has been also tested in AMD patients. We extended our analysis to a possible additional effect regulated by saffron and compared in AMD patients a pure antioxidant treatment (Lutein/zeaxanthin) with saffron treatment. Methods: Animal model. Sprague-Dawley (SD) adult rats, raised at 5 lux, were exposed to 1000 lux for 24 h and then either immediately sacrificed or placed back at 5 lux for 7 days recovery period. A group of animals was treated with saffron. We performed in the animal model: (1) SDS-PAGE analysis; (2) Western Blotting (3) Enzyme activity assay (4) Immunolabelling; in AMD patients: a longitudinal open-label study 29 (+/- 5) months in two groups of patients: lutein/zeaxanthin (19) and saffron (23) treated. Visual function was tested every 8 months by ERG recordings in addition to clinical examination. Results: Enzymatic activity of MMP-3 is reduced in LD saffron treated retinas and is comparable to control as it is MMP-3 expression. LD treated retinas do not present "rosettes" and microglia activation and migration is highly reduced. Visual function remains stable in saffron treated AMD patients while deteriorates in the lutein/zeaxanthin group. Conclusion: Our results provide evidence of an additional way of action of saffron treatment confirming the complex nature of neuroprotective activities of its chemical components. Accordingly, long term follow-up in AMD patients reveals an added value of saffron supplementation treatment compared to classical antioxidant protocol

Mechanisms of photoreceptor death and survival in mammalian retina

The mammalian retina, like the rest of the central nervous system, is highly stable and can maintain its structure and function for the full life of the individual, in humans for many decades. Photoreceptor dystrophies are instances of retinal instability. Many are precipitated by genetic mutations and scores of photoreceptor-lethal mutations have now been identified at the codon level. This review explores the factors which make the photoreceptor more vulnerable to small mutations of its proteins than any other cell of the body, and more vulnerable to environmental factors than any other retinal neurone. These factors include the highly specialised structure and function of the photoreceptors, their high appetite for energy, their self-protective mechanisms and the architecture of their energy supply from the choroidal circulation. Particularly important are the properties of the choroidal circulation, especially its fast flow of near-arterial blood and its inability to autoregulate. Mechanisms which make the retina stable and unstable are then reviewed in three different models of retinal degeneration, retinal detachment, photoreceptor dystrophy and light damage. A two stage model of the genesis of photoreceptor dystrophies is proposed, comprising an initial "depletion" stage caused by genetic or environmental insult and a second "late" stage during which oxygen toxicity damages and eventually destroys any photoreceptors which survive the initial depletion. It is a feature of the model that the second "late" stage of retinal dystrophies is driven by oxygen toxicity. The implications of these ideas for therapy of retinal dystrophies are discussed