Loss of CLN3, the gene mutated in juvenile neuronal ceroid lipofuscinosis, leads to metabolic impairment and autophagy induction in retinal pigment epithelium.

Juvenile neuronal ceroid lipofuscinosis (JNCL, aka. juvenile Batten disease or CLN3 disease) is a lysosomal storage disease characterized by progressive blindness, seizures, cognitive and motor failures, and premature death. JNCL is caused by mutations in the Ceroid Lipofuscinosis, Neuronal 3 (CLN3) gene, whose function is unclear. Although traditionally considered a neurodegenerative disease, CLN3 disease displays eye-specific effects: Vision loss not only is often one of the earliest symptoms of JNCL, but also has been reported in non-syndromic CLN3 disease. Here we described the roles of CLN3 protein in maintaining healthy retinal pigment epithelium (RPE) and normal vision. Using electroretinogram, fundoscopy and microscopy, we showed impaired visual function, retinal autofluorescent lesions, and RPE disintegration and metaplasia/hyperplasia in a Cln3 ~ 1 kb-deletion mouse model [1] on C57BL/6J background. Utilizing a combination of biochemical analyses, RNA-Seq, Seahorse XF bioenergetic analysis, and Stable Isotope Resolved Metabolomics (SIRM), we further demonstrated that loss of CLN3 increased autophagic flux, suppressed mTORC1 and Akt activities, enhanced AMPK activity, and up-regulated gene expression of the autophagy-lysosomal system in RPE-1 cells, suggesting autophagy induction. This CLN3 deficiency induced autophagy induction coincided with decreased mitochondrial oxygen consumption, glycolysis, the tricarboxylic acid (TCA) cycle, and ATP production. We also reported for the first time that loss of CLN3 led to glycogen accumulation despite of impaired glycogen synthesis. Our comprehensive analyses shed light on how loss of CLN3 affect autophagy and metabolism. This work suggests possible links among metabolic impairment, autophagy induction and lysosomal storage, as well as between RPE atrophy/degeneration and vision loss in JNCL.

Conveying facial expressions to blind and visually impaired persons through a wearable vibrotactile device.

In face-to-face social interactions, blind and visually impaired persons (VIPs) lack access to nonverbal cues like facial expressions, body posture, and gestures, which may lead to impaired interpersonal communication. In this study, a wearable sensory substitution device (SSD) consisting of a head mounted camera and a haptic belt was evaluated to determine whether vibrotactile cues around the waist could be used to convey facial expressions to users and whether such a device is desired by VIPs for use in daily living situations. Ten VIPs (mean age: 38.8, SD: 14.4) and 10 sighted persons (SPs) (mean age: 44.5, SD: 19.6) participated in the study, in which validated sets of pictures, silent videos, and videos with audio of facial expressions were presented to the participant. A control measurement was first performed to determine how accurately participants could identify facial expressions while relying on their functional senses. After a short training, participants were asked to determine facial expressions while wearing the emotion feedback system. VIPs using the device showed significant improvements in their ability to determine which facial expressions were shown. A significant increase in accuracy of 44.4% was found across all types of stimuli when comparing the scores of the control (mean±SEM: 35.0±2.5%) and supported (mean±SEM: 79.4±2.1%) phases. The greatest improvements achieved with the support of the SSD were found for silent stimuli (68.3% for pictures and 50.8% for silent videos). SPs also showed consistent, though not statistically significant, improvements while supported. Overall, our study shows that vibrotactile cues are well suited to convey facial expressions to VIPs in real-time. Participants became skilled with the device after a short training session. Further testing and development of the SSD is required to improve its accuracy and aesthetics for potential daily use.

Lateral geniculate neurons projecting to primary visual cortex show ocular dominance plasticity in adult mice.

Experience-dependent plasticity in the mature visual system is widely considered to be cortical. Using chronic two-photon Ca2+ imaging of thalamic afferents in layer 1 of binocular visual cortex, we provide evidence against this tenet: the respective dorsal lateral geniculate nucleus (dLGN) cells showed pronounced ocular dominance (OD) shifts after monocular deprivation in adult mice. Most (86%), but not all, of dLGN cell boutons were monocular during normal visual experience. Following deprivation, initially deprived-eye-dominated boutons reduced or lost their visual responsiveness to that eye and frequently became responsive to the non-deprived eye. This cannot be explained by eye-specific cortical changes propagating to dLGN via cortico-thalamic feedback because the shift in dLGN responses was largely resistant to cortical inactivation using the GABAA receptor agonist muscimol. Our data suggest that OD shifts observed in the binocular visual cortex of adult mice may at least partially reflect plasticity of eye-specific inputs onto dLGN neurons.

Thalamocortical Connectivity and Microstructural Changes in Congenital and Late Blindness.

There is ample evidence that the occipital cortex of congenitally blind individuals processes nonvisual information. It remains a debate whether the cross-modal activation of the occipital cortex is mediated through the modulation of preexisting corticocortical projections or the reorganisation of thalamocortical connectivity. Current knowledge on this topic largely stems from anatomical studies in animal models. The aim of this study was to test whether purported changes in thalamocortical connectivity in blindness can be revealed by tractography based on diffusion-weighted magnetic resonance imaging. To assess the thalamocortical network, we used a clustering method based on the thalamic white matter projections towards predefined cortical regions. Five thalamic clusters were obtained in each group representing their cortical projections. Although we did not find differences in the thalamocortical network between congenitally blind individuals, late blind individuals, and normal sighted controls, diffusion tensor imaging (DTI) indices revealed significant microstructural changes within thalamic clusters of both blind groups. Furthermore, we find a significant decrease in fractional anisotropy (FA) in occipital and temporal thalamocortical projections in both blind groups that were not captured at the network level. This suggests that plastic microstructural changes have taken place, but not in a degree to be reflected in the tractography-based thalamocortical network.

Neural correlates of audiotactile phonetic processing in early-blind readers: an fMRI study.

Reading is a multisensory function that relies on arbitrary associations between auditory speech sounds and symbols from a second modality. Studies of bimodal phonetic perception have mostly investigated the integration of visual letters and speech sounds. Blind readers perform an analogous task by using tactile Braille letters instead of visual letters. The neural underpinnings of audiotactile phonetic processing have not been studied before. We used functional magnetic resonance imaging to reveal the neural correlates of audiotactile phonetic processing in 16 early-blind Braille readers. Braille letters and corresponding speech sounds were presented in unimodal, and congruent/incongruent bimodal configurations. We also used a behavioral task to measure the speed of blind readers in identifying letters presented via tactile and/or auditory modalities. Reaction times for tactile stimuli were faster. The reaction times for bimodal stimuli were equal to those for the slower auditory-only stimuli. fMRI analyses revealed the convergence of unimodal auditory and unimodal tactile responses in areas of the right precentral gyrus and bilateral crus I of the cerebellum. The left and right planum temporale fulfilled the 'max criterion' for bimodal integration, but activities of these areas were not sensitive to the phonetical congruency between sounds and Braille letters. Nevertheless, congruency effects were found in regions of frontal lobe and cerebellum. Our findings suggest that, unlike sighted readers who are assumed to have amodal phonetic representations, blind readers probably process letters and sounds separately. We discuss that this distinction might be due to mal-development of multisensory neural circuits in early blinds or it might be due to inherent differences between Braille and print reading mechanisms.

Reading in the dark: neural correlates and cross-modal plasticity for learning to read entire words without visual experience.

Cognitive neuroscience has long attempted to determine the ways in which cortical selectivity develops, and the impact of nature vs. nurture on it. Congenital blindness (CB) offers a unique opportunity to test this question as the brains of blind individuals develop without visual experience. Here we approach this question through the reading network. Several areas in the visual cortex have been implicated as part of the reading network, and one of the main ones among them is the VWFA, which is selective to the form of letters and words. But what happens in the CB brain? On the one hand, it has been shown that cross-modal plasticity leads to the recruitment of occipital areas, including the VWFA, for linguistic tasks. On the other hand, we have recently demonstrated VWFA activity for letters in contrast to other visual categories when the information is provided via other senses such as touch or audition. Which of these tasks is more dominant? By which mechanism does the CB brain process reading? Using fMRI and visual-to-auditory sensory substitution which transfers the topographical features of the letters we compare reading with semantic and scrambled conditions in a group of CB. We found activation in early auditory and visual cortices during the early processing phase (letter), while the later phase (word) showed VWFA and bilateral dorsal-intraparietal activations for words. This further supports the notion that many visual regions in general, even early visual areas, also maintain a predilection for task processing even when the modality is variable and in spite of putative lifelong linguistic cross-modal plasticity. Furthermore, we find that the VWFA is recruited preferentially for letter and word form, while it was not recruited, and even exhibited deactivation, for an immediately subsequent semantic task suggesting that despite only short sensory substitution experience orthographic task processing can dominate semantic processing in the VWFA. On a wider scope, this implies that at least in some cases cross-modal plasticity which enables the recruitment of areas for new tasks may be dominated by sensory independent task specific activation.

Relationship Between Cortical Thickness and Functional Activation in the Early Blind.

Early blindness results in both structural and functional changes of the brain. However, these changes have rarely been studied in relation to each other. We measured alterations in cortical thickness (CT) caused by early visual deprivation and their relationship with cortical activity. Structural and functional magnetic resonance imaging was performed in 12 early blind (EB) humans and 12 sighted controls (SC). Experimental conditions included one-back tasks for auditory localization and pitch identification, and a simple sound-detection task. Structural and functional data were analyzed in a whole-brain approach and within anatomically defined regions of interest in sensory areas of the spared (auditory) and deprived (visual) modalities. Functional activation during sound-localization or pitch-identification tasks correlated negatively with CT in occipital areas of EB (calcarine sulcus, lingual gyrus, superior and middle occipital gyri, and cuneus) and in nonprimary auditory areas of SC. These results suggest a link between CT and activation and demonstrate that the relationship between cortical structure and function may depend on early sensory experience, probably via selective pruning of exuberant connections. Activity-dependent effects of early sensory deprivation and long-term practice are superimposed on normal maturation and aging. Together these processes shape the relationship between brain structure and function over the lifespan.

Ex vivo expansion of bovine corneal endothelial cells in xeno-free medium supplemented with platelet releasate.

Clinical-grade ex vivo expansion of corneal endothelial cells can increase the availability of corneal tissues for transplantation and treatment of corneal blindness. However, these cells have very limited proliferative capacity. Successful propagation has required so far to use very complex growth media supplemented with fetal bovine serum and other xenocomponents. We hypothesized that human platelet releasates rich in multiple growth factors, and in particular neurotrophins, could potentially be a useful supplement for ex vivo expansion of corneal endothelium cells due to their neural crest origin. Platelet releasates were prepared by calcium salt activation of apheresis platelet concentrates, subjected or not to complement inactivation by heat treatment at 56°C for 30 minutes. Platelet releasates were characterized for their content in proteins and were found to contain high amount of growth factors including platelet-derived growth factor-AB (30.56 to 39.08 ng/ml) and brain-derived neurotrophic factor (30.57 to 37.11 ng/ml) neurotrophins. We compared the growth and viability of corneal endothelium cells in DMEM-F12 medium supplemented with different combinations of components, including 2.5%∼10% of the platelet releasates. Corneal endothelium cells expanded in platelet releasates exhibited good adhesion and a typical hexagonal morphology. Their growth and viability were enhanced when using the complement-inactivated platelet releasate at a concentration of 10%. Immunostaining and Western blots showed that CECs maintained the expressions of four important membrane markers: Na-K ATPase α1, zona occludens-1, phospho-connexin 43 and N-cadherin. In conclusion, our study provides the first proof-of-concept that human platelet releasates can be used for ex vivo expansion of corneal endothelium cells. These findings open a new paradigm for ex vivo propagation protocols of corneal endothelium cells in compliance with good tissue culture practices and regulatory recommendations to limit the use of xenogenic materials.

Impact of blindness onset on the functional organization and the connectivity of the occipital cortex.

Contrasting the impact of congenital versus late-onset acquired blindness provides a unique model to probe how experience at different developmental periods shapes the functional organization of the occipital cortex. We used functional magnetic resonance imaging to characterize brain activations of congenitally blind, late-onset blind and two groups of sighted control individuals while they processed either the pitch or the spatial attributes of sounds. Whereas both blind groups recruited occipital regions for sound processing, activity in bilateral cuneus was only apparent in the congenitally blind, highlighting the existence of region-specific critical periods for crossmodal plasticity. Most importantly, the preferential activation of the right dorsal stream (middle occipital gyrus and cuneus) for the spatial processing of sounds was only observed in the congenitally blind. This demonstrates that vision has to be lost during an early sensitive period in order to transfer its functional specialization for space processing toward a non-visual modality. We then used a combination of dynamic causal modelling with Bayesian model selection to demonstrate that auditory-driven activity in primary visual cortex is better explained by direct connections with primary auditory cortex in the congenitally blind whereas it relies more on feedback inputs from parietal regions in the late-onset blind group. Taken together, these results demonstrate the crucial role of the developmental period of visual deprivation in (re)shaping the functional architecture and the connectivity of the occipital cortex. Such findings are clinically important now that a growing number of medical interventions may restore vision after a period of visual deprivation.

Tool selectivity in left occipitotemporal cortex develops without vision.

Previous studies have provided evidence for a tool-selective region in left lateral occipitotemporal cortex (LOTC). This region responds selectively to pictures of tools and to characteristic visual tool motion. The present human fMRI study tested whether visual experience is required for the development of tool-selective responses in left LOTC. Words referring to tools, animals, and nonmanipulable objects were presented auditorily to 14 congenitally blind and 16 sighted participants. Sighted participants additionally viewed pictures of these objects. In whole-brain group analyses, sighted participants showed tool-selective activity in left LOTC in both visual and auditory tasks. Importantly, virtually identical tool-selective LOTC activity was found in the congenitally blind group performing the auditory task. Furthermore, both groups showed equally strong tool-selective activity for auditory stimuli in a tool-selective LOTC region defined by the picture-viewing task in the sighted group. Detailed analyses in individual participants showed significant tool-selective LOTC activity in 13 of 14 blind participants and 14 of 16 sighted participants. The strength and anatomical location of this activity were indistinguishable across groups. Finally, both blind and sighted groups showed significant resting state functional connectivity between left LOTC and a bilateral frontoparietal network. Together, these results indicate that tool-selective activity in left LOTC develops without ever having seen a tool or its motion. This finding puts constraints on the possible role that this region could have in tool processing and, more generally, provides new insights into the principles shaping the functional organization of OTC.

Shape-specific activation of occipital cortex in an early blind echolocation expert.

We have previously reported that an early-blind echolocating individual (EB) showed robust occipital activation when he identified distant, silent objects based on echoes from his tongue clicks (Thaler, Arnott, & Goodale, 2011). In the present study we investigated the extent to which echolocation activation in EB's occipital cortex reflected general echolocation processing per se versus feature-specific processing. In the first experiment, echolocation audio sessions were captured with in-ear microphones in an anechoic chamber or hallway alcove as EB produced tongue clicks in front of a concave or flat object covered in aluminum foil or a cotton towel. All eight echolocation sessions (2 shapes×2 surface materials×2 environments) were then randomly presented to him during a sparse-temporal scanning fMRI session. While fMRI contrasts of chamber versus alcove-recorded echolocation stimuli underscored the importance of auditory cortex for extracting echo information, main task comparisons demonstrated a prominent role of occipital cortex in shape-specific echo processing in a manner consistent with latent, multisensory cortical specialization. Specifically, relative to surface composition judgments, shape judgments elicited greater BOLD activity in ventrolateral occipital areas and bilateral occipital pole. A second echolocation experiment involving shape judgments of objects located 20° to the left or right of straight ahead activated more rostral areas of EB's calcarine cortex relative to location judgments of those same objects and, as we previously reported, such calcarine activity was largest when the object was located in contralateral hemispace. Interestingly, other echolocating experts (i.e., a congenitally blind individual in Experiment 1, and a late blind individual in Experiment 2) did not show the same pattern of feature-specific echo-processing calcarine activity as EB, suggesting the possible significance of early visual experience and early echolocation training. Together, our findings indicate that the echolocation activation in EB's occipital cortex is feature-specific, and that these object representations appear to be organized in a topographic manner.

Mutant NADH dehydrogenase subunit 4 gene delivery to mitochondria by targeting sequence-modified adeno-associated virus induces visual loss and optic atrophy in mice.

PURPOSE: Although mutated G11778A NADH ubiquinone oxidoreductase subunit 4 (ND4) mitochondrial DNA (mtDNA) is firmly linked to the blindness of Leber hereditary optic neuropathy (LHON), a bona fide animal model system with mutated mtDNA complex I subunits that would enable probing the pathogenesis of optic neuropathy and testing potential avenues for therapy has yet to be developed. METHODS: The mutant human ND4 gene with a guanine to adenine transition at position 11778 with an attached FLAG epitope under control of the mitochondrial heavy strand promoter (HSP) was inserted into a modified self-complementary (sc) adeno-associated virus (AAV) backbone. The HSP-ND4FLAG was directed toward the mitochondria by adding the 23 amino acid cytochrome oxidase subunit 8 (COX8) presequence fused in frame to the N-terminus of green fluorescent protein (GFP) into the AAV2 capsid open reading frame. The packaged scAAV-HSP mutant ND4 was injected into the vitreous cavity of normal mice (OD). Contralateral eyes received scAAV-GFP (OS). Translocation and integration of mutant human ND4 in mouse mitochondria were assessed with PCR, reverse transcription-polymerase chain reaction (RT-PCR), sequencing, immunoblotting, and immunohistochemistry. Visual function was monitored with serial pattern electroretinography (PERG) and in vivo structure with spectral domain optical coherence tomography (OCT). Animals were euthanized at 1 year and processed for light and transmission electron microscopy. RESULTS: The PCR products of the mitochondrial and nuclear DNA extracted from infected retinas and optic nerves gave the expected 500 base pair bands. RT-PCR confirmed transcription of the mutant human ND4 DNA in mice. DNA sequencing confirmed that the PCR and RT-PCR products were mutant human ND4 (OD only). Immunoblotting revealed the expression of mutant ND4FLAG (OD only). Pattern electroretinograms showed a significant decrement in retinal ganglion cell function OD relative to OS at 1 month and 6 months after AAV injections. Spectral domain optical coherence tomography showed optic disc edema starting at 1 month post injection followed by optic nerve head atrophy with marked thinning of the inner retina at 1 year. Histopathology of optic nerve cross sections revealed reductions in the optic nerve diameters of OD versus OS where transmission electron microscopy revealed significant loss of optic nerve axons in mutant ND4 injected eyes where some remaining axons were still in various stages of irreversible degeneration with electron dense aggregation. Electron lucent mitochondria accumulated in swollen axons where fusion of mitochondria was also evident. CONCLUSIONS: Due to the UGA codon at amino acid 16, mutant G11778A ND4 was translated only in the mitochondria where its expression led to significant loss of visual function, loss of retinal ganglion cells, and optic nerve degeneration recapitulating the hallmarks of human LHON.

Dietary antioxidants prevent age-related retinal pigment epithelium actin damage and blindness in mice lacking αvß5 integrin.

In the aging human eye, oxidative damage and accumulation of pro-oxidant lysosomal lipofuscin cause functional decline of the retinal pigment epithelium (RPE), which contributes to age-related macular degeneration. In mice with an RPE-specific phagocytosis defect due to lack of αvß5 integrin receptors, RPE accumulation of lipofuscin suggests that the age-related blindness we previously described in this model may also result from oxidative stress. Cellular and molecular targets of oxidative stress in the eye remain poorly understood. Here we identify actin among 4-hydroxynonenal (HNE) adducts formed specifically in ß5(-/-) RPE but not in neural retina with age. HNE modification directly correlated with loss of resistance of actin to detergent extraction, suggesting cytoskeletal damage in aging RPE. Dietary enrichment with natural antioxidants, grapes or marigold extract containing macular pigments lutein/zeaxanthin, was sufficient to prevent HNE-adduct formation, actin solubility, lipofuscin accumulation, and age-related cone and rod photoreceptor dysfunction in ß5(-/-) mice. Acute generation of HNE adducts directly destabilized actin but not tubulin cytoskeletal elements of RPE cells. These findings identify destabilization of the actin cytoskeleton as a consequence of a physiological, sublethal oxidative burden of RPE cells in vivo that is associated with age-related blindness and that can be prevented by consuming an antioxidant-rich diet.

Activation of the occipital cortex and deactivation of the default mode network during working memory in the early blind.

Although blind people heavily depend on working memory to manage daily life without visual information, it is not clear yet whether their working memory processing involves functional reorganization of the memory-related cortical network. To explore functional reorganization of the cortical network that supports various types of working memory processes in the early blind, we investigated activation differences between 2-back tasks and 0-back tasks using fMRI in 10 congenitally blind subjects and 10 sighted subjects. We used three types of stimulus sequences: words for a verbal task, pitches for a non-verbal task, and sound locations for a spatial task. When compared to the sighted, the blind showed additional activations in the occipital lobe for all types of stimulus sequences for working memory and more significant deactivation in the posterior cingulate cortex of the default mode network. The blind had increased effective connectivity from the default mode network to the left parieto-frontal network and from the occipital cortex to the right parieto-frontal network during the 2-back tasks than the 0-back tasks. These findings suggest not only cortical plasticity of the occipital cortex but also reorganization of the cortical network for the executive control of working memory.

Preserved functional specialization for spatial processing in the middle occipital gyrus of the early blind.

The occipital cortex (OC) of early-blind humans is activated during various nonvisual perceptual and cognitive tasks, but little is known about its modular organization. Using functional MRI we tested whether processing of auditory versus tactile and spatial versus nonspatial information was dissociated in the OC of the early blind. No modality-specific OC activation was observed. However, the right middle occipital gyrus (MOG) showed a preference for spatial over nonspatial processing of both auditory and tactile stimuli. Furthermore, MOG activity was correlated with accuracy of individual sound localization performance. In sighted controls, most of extrastriate OC, including the MOG, was deactivated during auditory and tactile conditions, but the right MOG was more activated during spatial than nonspatial visual tasks. Thus, although the sensory modalities driving the neurons in the reorganized OC of blind individuals are altered, the functional specialization of extrastriate cortex is retained regardless of visual experience.

Cortical activity during tactile exploration of objects in blind and sighted humans.

PURPOSE: Recent studies show evidence of multisensory representation in the functionally normal visual cortex, but this idea remains controversial. Occipital cortex activation is often claimed to be a reflection of mental visual imagery processes triggered by other modalities. However, if the occipital cortex is genuinely active during touch, this might be the basis for the massive cross-modal plasticity observed in the congenitally blind. METHODS: To address these issues, we used fMRI to compare patterns of activation evoked by a tactile object recognition (TOR) task (right or left hand) in 8 sighted and 8 congenitally blind subjects, with several other control tasks. RESULTS: TOR robustly activated object selective regions in the lateral occipital complex (LOC/LOtv) in the blind (similar to the patterns of activation found in the sighted), indicating that object identification per se (i.e. in the absence of visual imagery) is sufficient to evoke responses in the LOC/LOtv. Importantly, there was negligible occipital activation for hand movements (imitating object palpations) in the occipital cortex, in both groups. Moreover, in both groups, TOR activation in the LOC/LOtv was bilateral, regardless of the palpating hand (similar to the lack of strong visual field preference in the LOC/LOtv for viewed objects). Finally, the most prominent enhancement in TOR activation in the congenitally blind (compared to their sighted peers) was found in the posterior occipital cortex. CONCLUSIONS: These findings suggest that visual imagery is not an obligatory condition for object activation in visual cortex. It also demonstrates the massive plasticity in visual cortex of the blind for tactile object recognition that involves both the ventral and dorsal occipital areas, probably to support the high demand for this function in the blind.

Category-specific organization in the human brain does not require visual experience.

Distinct regions within the ventral visual pathway show neural specialization for nonliving and living stimuli (e.g., tools, houses versus animals, faces). The causes of these category preferences are widely debated. Using functional magnetic resonance imaging, we find that the same regions of the ventral stream that show category preferences for nonliving stimuli and animals in sighted adults show the same category preferences in adults who are blind since birth. Both blind and sighted participants had larger blood oxygen-level dependent (BOLD) responses in the medial fusiform gyrus for nonliving stimuli compared to animal stimuli and differential BOLD responses in lateral occipital cortex for animal stimuli compared to nonliving stimuli. These findings demonstrate that the medial-to-lateral bias by conceptual domain in the ventral visual pathway does not require visual experience in order to develop and suggest the operation of innately determined domain-specific constraints on the organization of object knowledge.

Imagery and spatial processes in blindness and visual impairment.

The objective of this review is to examine and evaluate recent findings on cognitive functioning (in particular imagery processes) in individuals with congenital visual impairments, including total blindness, low-vision and monocular vision. As one might expect, the performance of blind individuals in many behaviours and tasks requiring imagery can be inferior to that of sighted subjects; however, surprisingly often this is not the case. Interestingly, there is evidence that the blind often employ different cognitive mechanisms than sighted subjects, suggesting that compensatory mechanisms can overcome the limitations of sight loss. Taken together, these studies suggest that the nature of perceptual input on which we commonly rely strongly affects the organization of our mental processes. We also review recent neuroimaging studies on the neural correlates of sensory perception and mental imagery in visually impaired individuals that have cast light on the plastic functional reorganization mechanisms associated with visual deprivation.

Regression of herpes viral infection symptoms using melatonin and SB-73: comparison with Acyclovir.

Infection with Herpes simplex virus type 1 (HSV-1) typically causes lesions of the mouth, face, skin, esophagus, or brain. Herpes simplex virus type 2 (HSV-2) usually causes infections of the genitals, rectum, skin, hands, or meninges. The herpes viruses are a major cause of blindness from keratitis. The usual drugs used for herpes are Vidarabine, Acyclovir, Penciclovir and Ganciclovir; they are associated with several complications. The aim of this study was to investigate if a formulation containing 2.5 mg melatonin and 100 mg SB-73 would help patients with herpes, and to compare the preparation with 200 mg Acyclovir. SB-73 is a mixture of magnesium, phosphate, fatty acids extracted from Aspergillus sp. which has anti-herpes virus properties. A single blind randomized study was performed in which 70 patients underwent treatment using the supplement cited above (group A) and 75 received treatment of 200 mg Acyclovir (group B). Sixty-seven patients of the group A (95.7%) reported a complete regression of symptoms after 7 days of treatment. By comparison, 64 subjects (85.3%) of the Acyclovir reported regression of symptoms in the same period. There was statiscally significant difference between the groups (P < 0.05).