Search

International audience; Most inherited retinal dystrophies display progressive photoreceptor cell degeneration leading to severe visual impairment. Optogenetic reactivation of retinal neurons mediated by adeno-associated virus (AAV) gene therapy has the potential to restore vision regardless of patient-specific mutations. The challenge for clinical translatability is to restore a vision as close to natural vision as possible, while using a surgically safe delivery route for the fragile degenerated retina. To preserve the visual processing of the inner retina, we targeted ON bipolar cells, which are still present at late stages of disease. For safe gene delivery, we used a recently engineered AAV variant that can transduce the bipolar cells after injection into the eye's easily accessible vitreous humor. We show that AAV encoding channelrhodopsin under the ON bipolar cell-specific promoter mediates long-term gene delivery restricted to ON-bipolar cells after intravitreal administration. Channelrhodopsin expression in ON bipolar cells leads to restoration of ON and OFF responses at the retinal and cortical levels. Moreover, light-induced locomotory behavior is restored in treated blind mice. Our results support the clinical relevance of a minimally invasive AAV-mediated optogenetic therapy for visual restoration.

Summary Purpose To assess vision loss, identify affected anatomical sites, determine etiologies and potentially avoidable causes in students attending two institutions for the visually disabled in Tunis city. Methods A visit for a complete ophthalmological examination was performed. All students attending these schools were recruited in our study. The World Health Organisation Programme for the Prevention of Blindness (WHO/PBL) examination record for children was used. Data was analysed by the SPSS version 17 statistical software. Results A total of 172 students were recruited with mean age of 11.9 ± 3.3 years (between 6 and 18 years). One hundred and thirty-seven (79.6%) were under 16 years. The sex-ratio was 1.17. Ninety students (52.3%) had low vision and eighty-two (47.7%) were blind. We reported retina (29%), whole globe (29%), globe appears normal (11%) and optic nerve (9.8%) as the common sites of ocular abnormalities. Retinal dystrophy (22.7%) and congenital glaucoma (22.7%) were the most reported ocular diseases. The main etiologies were hereditary (54.1%) and unknown (30.8%). Consanguinity was reported in 108 students (62.8%), and fifty-five students (32%) had a positive family history. Overall, 50.5% (87/172) of ocular diseases were potentially treatable or preventable. Conclusion Retinal dystrophy and congenital glaucoma were the most common eye diseases. Heredity was the main etiology, and consanguinity was high. To decrease their incidence, awareness of the family members of the risks of consanguinous marriage and appropriate therapy for congenital glaucoma/cataract may significantly improve the child's visual prognosis.

International audience; Generic properties of curvature representations formed on the basis of vision and touch were examined as a function of mathematical properties of curved objects. Virtual representations of the curves were shown on a computer screen for visual scaling by sighted observers (experiment 1). Their physical counterparts were placed in the two hands of blindfolded and congenitally blind observers for tactile scaling. The psychophysical data show that curvature representations in congenitally blind individuals, who never had any visual experience, and in sighted observers, who rely on vision most of the time, are statistically linked to the same mathematical properties of the curves. The perceived magnitude of object curvature, sensed through either vision or touch, is related by a mathematical power law, with similar exponents for the two sensory modalities, to the aspect ratio of the curves, a scale invariant geometric property. This finding supports biologically motivated models of sensory integration suggesting a universal power law for the brain control and balance of motor responses to environmental stimuli from any sensory modality to inspire adaptive systems design.

International audience; BACKGROUND: Some previous studies have revealed that while congenitally blind people have a tendency to refer to visual attributes ('verbalism'), references to auditory and tactile attributes are scarcer. However, this statement may be challenged by current theories claiming that cognition is linked to the perceptions and actions from which it derives. Verbal productions by the blind could therefore differ from those of the sighted because of their specific perceptual experience. The relative weight of each sense in oral descriptions was compared in three groups with different visual experience Congenitally blind (CB), late blind (LB) and blindfolded sighted (BS) adults. METHODOLOGY/PRINCIPAL FINDINGS: Participants were asked to give an oral description of their mother and their father, and of four familiar manually-explored objects. The number of visual references obtained when describing people was relatively high, and was the same in the CB and BS groups ("verbalism" in the CB). While references to touch were scarce in all groups, the CB referred to audition more frequently than the LB and the BS groups. There were, by contrast, no differences between groups in descriptions of objects, and references to touch dominated the other modalities. CONCLUSION/SIGNIFICANCE: The relative weight of each modality varies according to the cognitive processes involved in each task. Long term memory, internal representations and information acquired through social communication, are at work in the People task, seem to favour visual references in both the blind and the sighted, whereas the congenitally blind also refer often to audition. By contrast, the perceptual encoding and working memory at work in the Objects task enhance sensory references to touch in a similar way in all groups. These results attenuate the impact of verbalism in blindness, and support (albeit moderately) the idea that the perceptual experience of the congenitally blind is to some extent reflected in their cognition.

Background: Trachoma, a chronic keratoconjunctivitis caused by Chlamydia trachomatis, is the world's commonest infectious cause of blindness. Blindness is due to progressive scarring of the conjunctiva (trachomatous scarring) leading to in-turning of eyelashes (trichiasis) and corneal opacification. We evaluated the contribution of genetic variation across the chemokine and cytokine clusters in chromosomes 4q and 5q31 respectively to risk of scarring trachoma and trichiasis in a large case-control association study in a Gambian population. Methods: Linkage disequilibrium (LD) mapping was used to investigate risk effects across the 4q and 5q31 cytokine clusters in relation to the risk of scarring sequelae of ocular Ct infection. Disease association and epistatic effects were assessed in a population based study of 651 case-control pairs by conditional logistic regression (CLR) analyses. Results: LD mapping suggested that genetic effects on risk within these regions mapped to the pro-inflammatory innate immune genes interleukin 8 (IL8) and granulocyte-macrophage colony stimulatory factor (CSF2) loci. The IL8-251 rare allele (IL8-251 TT) was associated with protection from scarring trachoma (OR = 0.29 p = 0.027). The intronic CSF2_27348 A allele in chromosome 5q31 was associated with dose dependent protection from trichiasis, with each copy of the allele reducing risk by 37% (p = 0.005). There was evidence of epistasis, with effects at IL8 and CSF2 loci interacting with those previously reported at the MMP9 locus, a gene acting downstream to IL8 and CSF2 in the inflammatory cascade. Conclusion: innate immune response SNP-haplotypes are linked to ocular Ct sequelae. This work illustrates the first example of epistatic effects of two genes on trachoma.

International audience; PURPOSE: To explore electrically induced phosphenes in blind patients with retinitis pigmentosa (RP) in comparison with healthy subjects and to develop a screening test for candidates for an optic nerve visual prosthesis implantation. METHODS: Phosphenes are obtained by charge balanced biphasic pulse stimulations through a surface cathode over the closed eyelids and an anode near the opposite ear. The resulting strength-duration relationship for somatosensory, phosphene, and pain threshold has been recorded in five RP patients as well as in 10 healthy volunteers. RESULTS: In sighted subjects, the average rheobase and chronaxy for phosphene perception are 0.28 mA and 3.07 msec, respectively. For pulse durations longer than 2 msec, phosphenes are usually obtained at current strengths below the level giving rise to any other electrically generated sensation. In RP patients, however, phosphenes are not so easily obtained. One in five had no visual response at all. Another patient reported a flash perception for the longest pulse durations only. Spontaneous phosphenes interfered heavily with the stimulation in a third person. Finally, despite the higher threshold, two patients displayed normally shaped strength-duration curves. CONCLUSIONS: The surface stimulation has proven harmless, adequate, and very helpful to ascertain that the optic nerve can be electrically activated in completely blind individuals. Long-duration stimulation pulses yield very low phosphene thresholds in healthy subjects. Anterior visual pathways activation requires higher currents in RP patients.

International audience; BACKGROUND: It has been shown that visual geometrical shape categories (rectangle and triangle) are graded structures organized around a prototype as demonstrated by perception and production tasks in adults as well as in children. The visual prototypical shapes are better recognized than other exemplars of the categories. Their existence could emerge from early exposure to these prototypical shapes that are present in our visual environment. The present study examined the role of visual experience in the existence of prototypical shapes by comparing the haptic recognition of geometrical shapes in congenitally blind and blindfolded adolescents. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether the existence of a prototype effect (higher recognition of prototypical shapes than non prototypical shapes) depended on visual experience, congenitally blind and blindfolded sighted adolescents were asked to recognize in the haptic modality three categories of correct shapes (square, rectangle, triangle) varying in orientation (prototypical/canonical orientation vs. non prototypical/canonical orientation rotated by 45°) among a set of other shapes. A haptic prototype effect was found in the blindfolded sighted whereas no difference between prototypical and non prototypical correct shapes was observed in the congenitally blind. A control experiment using a similar visual recognition task confirmed the existence of a visual prototype effect in a group of sighted adolescents. CONCLUSION/SIGNIFICANCE: These findings show that the prototype effect is not intrinsic to the haptic modality but depends on visual experience. This suggests that the occurrence of visual and haptic prototypical shapes in the recognition of geometrical shape seems to depend on visual exposure to these prototypical shapes existing in our environment.