Dysfunction of the magnocellular stream in Alzheimer's disease evaluated by pattern electroretinograms and visual evoked potentials

Background: Visuo-spatial disturbances could represent a clinical feature of early stage Alzheimer's disease (AD). The magnocellular (M) pathway has anatomo-physiological characteristic which make it more suitable for detecting form, motion and depth compared with parvocellular one (P). Objective: Aim of our study was to evaluate specific visual subsystem involvement in a group of AD patients, recording isoluminant chromatic and luminance pattern electroretinograms and pattern visual evoked potentials. Material and methods: data were obtained from 15 AD patients (9 females and 6 males, mean age \ub1 1SD: 77.6 \ub1 4.01 years) not yet undergoing any treatment, and from 10 age-matched healthy controls. Diagnosis of probable AD was clinically and neuroradiologically established. PERGs were recorded monocularly in response to equiluminant red-green (R-G), blue-yellow (B-Y) and luminance yellow-black (Y-Bk) horizontal square gratings of 0.3. c/deg and 90% contrast, reversed at 1. Hz. VEPs were recorded in response to full-field (14 deg) equiluminant chromatic R-G, B-Y and luminance Y-Bk sinusoidal gratings of 2. c/deg, presented in onset (300. ms)-offset (700. ms) mode, at the contrast levels of 90%. Results: All data were retrieved in terms of peak-amplitude and latency and assessed using the Student's t-test for paired data. Temporal differences of PERGs and VEPs, evoked by Y-Bk grating in AD patients compared with controls, suggest a specific impairment of the magnocellular stream. Conclusions: Our study support the hypothesis that the impairment of the PERGs and VEPs arising from the magnocellular streams of visual processing may indicate a primary dysfunction of the M-pathways in AD

A Novel High-Content Flow Cytometric Method for Assessing the Viability and Damage of Rat Retinal Ganglion Cells

PURPOSE: The aim of the study was to develop a high-content flow cytometric method for assessing the viability and damage of small, medium, and large retinal ganglion cells (RGCs) in N-methyl-D-aspartic acid (NMDA)-injury model. METHODS/RESULTS: Retinal toxicity was induced in rats by intravitreal injection of NMDA and RGCs were retrogradely labeled with Fluoro-Gold (FG). Seven days post-NMDA injection, flatmount and flow cytometric methods were used to evaluate RGCs. In addition, the RGC area diameter (D((a))) obtained from retinal flatmount imaging were plotted versus apparent volume diameter (D((v))) obtained from flow cytometry for the same cumulative cell number (sequentially from small to large RGCs) percentile (Q) to establish their relationship for accurately determining RGC sizes. Good correlation (r = 0.9718) was found between D((a)) and apparent D((v)). Both flatmount and flow cytometric analyses of RGCs showed that 40 mM NMDA significantly reduced the numbers of small and medium RGCs but not large RGCs. Additionally, flow cytometry showed that the geometric means of FG and thy-1 intensities in three types of RGCs decreased to 90.96±2.24% (P<0.05) and 91.78±1.89% (P>0.05) for small, 69.62±2.11% (P<0.01) and 69.07±2.98% (P<0.01) for medium, and 69.68±6.48% (P<0.05) and 69.91±6.23% (P<0.05) for large as compared with the normal RGCs. CONCLUSION: The established flow cytometric method provides high-content analysis for differential evaluation of RGC number and status and should be useful for the evaluation of various models of optic nerve injury and the effects of potential neuroprotective agents

Loss of Arc renders the visual cortex impervious to the effects of sensory experience or deprivation

A myriad of mechanisms have been suggested to account for the full richness of visual cortical plasticity. We found that visual cortex lacking Arc is impervious to the effects of deprivation or experience. Using intrinsic signal imaging and chronic visually evoked potential recordings, we found that Arc−/− mice did not exhibit depression of deprived-eye responses or a shift in ocular dominance after brief monocular deprivation. Extended deprivation also failed to elicit a shift in ocular dominance or open-eye potentiation. Moreover, Arc−/− mice lacked stimulus-selective response potentiation. Although Arc−/− mice exhibited normal visual acuity, baseline ocular dominance was abnormal and resembled that observed after dark-rearing. These data suggest that Arc is required for the experience-dependent processes that normally establish and modify synaptic connections in visual cortex.Howard Hughes Medical InstituteNational Science Foundation (U.S.

Psychoneuroimmunology: application to ocular diseases

Psychoneuroimmunology (PNI) is a relatively new discipline within the field of neuroscience which researches the relationship between emotional states, the central and peripheral nervous systems, and the endocrine and immune systems. Negative psychological states, such as stress, anxiety, and depression, may alter immune system regulation and modulation of peripheral cytokines. A plethora of PNI studies have shown that increased psychological stress and depression are associated with an alteration of immune functioning and worsened health outcomes for many conditions. To date, application of PNI methodology has not been reported for ocular diseases. This article provides an historical perspective on the origins of the rift between the emotional and spiritual from physical aspects of disease. A review of how stress is mediated through sympathetic adrenomedullary and hypothalamic pituitary axis activation with shifts in immunity is provided. The literature which supports spirituality in healing is presented. Finally, ocular diseases which would be most amenable to a PNI approach are discussed

Fragile x syndrome and autism: from disease model to therapeutic targets

Autism is an umbrella diagnosis with several different etiologies. Fragile X syndrome (FXS), one of the first identified and leading causes of autism, has been modeled in mice using molecular genetic manipulation. These Fmr1 knockout mice have recently been used to identify a new putative therapeutic target, the metabotropic glutamate receptor 5 (mGluR5), for the treatment of FXS. Moreover, mGluR5 signaling cascades interact with a number of synaptic proteins, many of which have been implicated in autism, raising the possibility that therapeutic targets identified for FXS may have efficacy in treating multiple other causes of autism

Visual-Evoked Potentials to Onset of Chromatic Red-Green and Blue-Yellow Gratings in Parkinson’s Disease Never Treated With L-Dopa

The differential dysfunction of chromatic and achromatic visual pathways in early Parkinson’s disease (PD) was evaluated by means of visual-evoked potentials (VEPs) recorded in 12 patients (mean age 60.1 ± 8.3 years; range 46 to 74 years) in the early stages of PD and not yet undergoing treatment with L-dopa, and in 12 age-matched controls. Visual stimuli were full-field (14 deg) equiluminant red-green (R-G), blue-yellow (B-Y), and black-white (B-W) sinusoidal gratings of two cycles per degree, presented in onset (300 milliseconds) – offset (700 milliseconds) mode, at two contrast (K) levels (90% and 25%). The VEP mean latencies were significantly more delayed in PD patients than in controls for chromatic than for luminance stimuli, in particular for B-Y stimuli of low contrast (K90%: B-W =6.6 milliseconds, R-G =3.34 milliseconds, B-Y =15.48 milliseconds; K25%: B-W =7.8 milliseconds, R-G =14.8 milliseconds, B-Y =28.9). Latencies of chromatic VEPs were more variable that achromatic VEP latencies in both normal subjects and PD patients. Therefore, the frequency of latency abnormalities (within 30%) was not significantly different for the three visual stimuli. Our results show that, in addition to achromatic VEPs, chromatic VEPs are impaired in early PD patients not yet undergoing L-dopa therapy, indicating an acquired color deficiency in these patients. The greater delay for the B-Y VEPs suggests a higher vulnerability of visual blue-cone pathway in the early stages of the disease. However, the overall sensitivity of chromatic VEPs in detecting early visual impairment in PD is comparable with that of achromatic VEPs