Retinitis pigmentosa

PURPOSE. To correlate the dimension of the visual field (VF) tested by Goldman kinetic perimetry with the extent of visi- bility of the highly reflective layer between inner and outer segments of photoreceptors (IOS) seen in optical coherence tomography (OCT) images in patients with retinitis pigmen- tosa (RP). METHODS. In a retrospectively designed cross-sectional study, 18 eyes of 18 patients

Recent advances in optogenetics and gene therapy have led to promising new treatment strategies for blindness caused by retinal photoreceptor loss. Preclinical studies often rely on the retinal degeneration 1 (rd1 or Pde6b(rd1)) retinitis pigmentosa (RP) mouse model. The rd1 founder mutation is present in more than 100 actively used mouse lines. Since secondary genetic traits are well-known to modify the phenotypic progression of photoreceptor degeneration in animal models and human patients with RP, negligence of the genetic background in the rd1 mouse model is unwarranted. Moreover, the success of various potential therapies, including optogenetic gene therapy and prosthetic implants, depends on the progress of retinal degeneration, which might differ between rd1 mice. To examine the prospect of phenotypic expressivity in the rd1 mouse model, we compared the progress of retinal degeneration in two common rd1 lines, C3H/HeOu and FVB/N. We followed retinal degeneration over 24 weeks...

The aim of this review is to introduce the reader to the world of clinical veterinary electroretinography. An important indication for ERG recordings in the dog is the early diagnosis of progressive retinal atrophy, an inherited form of photoreceptor degeneration, analogous to retinitis pigmentosa in humans. In most of the 20 canine breeds in which the disease has been studied electrophysiologically, changes in the ERG appear long before the appearance of clinical signs. This early diagnosis is a vital tool in efforts to eradicate the disease through preventive breeding. Pre-operative screening of canine cataract patients is another common indication for electroretinography in the dog. The ERG is also used to diagnose inherited and nutritional photoreceptor degenerations in the cat, and retinal disorders in a number of other animal species. The abundance of animal species (and breeds) seen by the veterinary ophthalmologist lends additional importance to the problem of a harmonized E...

Cet article ne peut en aucun cas remplacer les informations données par une consultation chez un médecin spécialiste. Certains points peuvent en effet paraitre obscurs au grand public ou être mal compris. Chaque patient étant un cas particulier nous recommandons aux patients qui présenteraient cette affection de s’adresser à leur médecin spécialiste qui seul peut établir un diagnostic et expliquer la maladie, sa forme et son évolution.

Retinitis pigmentosa is a group of inherited retinal diseases, which is bilateral and slowly progressive. It gradually involves the different histological layers of the retina. Although the whole retina will become affected, the disease usually starts in the retinal periphery. The first signs and symptoms are night blindness, restriction of the visual field and peripheral pigment epithelial changes. It may appear in childhood or later on, be generalized or more localized, with variable pigmentation and severity and be isolated or sometimes associated with systemic manifestations.

Cet article ne peut en aucun cas remplacer les informations données par une consultation chez un médecin spécialiste. Certains points peuvent en effet paraître obscurs au grand public ou être mal compris. Chaque patient étant un cas particulier nous recommandons aux patients qui présenteraient cette affection de s’adresser à leur médecin spécialiste qui seul peut établir un diagnostic et expliquer la maladie, sa forme et son évolution.

Bardet Biedl syndrome is a ciliopathy with multivisceral abnormalities, characterized by cone-rod dystrophy or rod-cone dystrophy, postaxial polydactyly, cognitive impairment, truncal obesity, renal malformation and hypogenitalism. The postaxial polydactyly is the most obvious external characteristic of the disease, already seen at birth. It is not always present and is not specific. Retinal dystrophy is constant but is not diagnosed immediately. There may be more or less severe forms with more or less early appearance. The retinal dystrophy is classically of the mixed rod-cone type. However, the macula may be involved in an early stage and the ERG will rather be of the cone-rod type.

We previously demonstrated that subretinal injection (SRI) of isogenic mesenchymal stem cells (MSCs) reduced the severity of retinal degeneration in Royal College of Surgeons rats in a focal manner. In contrast, intravenous MSC infusion (MSC IV) produced panoptic retinal rescue. By combining these treatments, we now show that MSC IV supplementation potentiates the MSC SRI-mediated rescue of photoreceptors and visual function. Electrophysiological recording from superior colliculi revealed 3.9-fold lower luminance threshold responses (LTRs) and 22% larger functional rescue area from combined treatment compared with MSC SRI alone. MSC IV supplementation of sham (saline) injection also improved LTRs 3.4-fold and enlarged rescue areas by 27% compared with saline alone. We confirmed the involvement of MSC chemotaxis for vision rescue by modulating C-X-C chemo-kine receptor 4 activity before MSC IV but without increased retinal homing. Rather, circulating platelets and lymphocytes were reduced 3 and 7 days after MSC IV , respectively. We demonstrated MSC SRI-mediated paracrine support of vision rescue by SRI of concentrated MSC-conditioned medium and assessed function by electroretinography and optokinetic response. MSC-secreted pep-tides increased retinal pigment epithelium (RPE) metabolic activity and clearance of photoreceptor outer segments ex vivo, which was partially abrogated by antibody blockade of trophic factors in concentrated MSC-conditioned medium, or their cognate receptors on RPE. These data support multimodal mechanisms for MSC-mediated retinal protection that differ by administration route and synergize when combined. Thus, using MSC IV as adjuvant therapy might improve cell therapies for retinal dystrophy and warrants further translational evaluation. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1–14 SIGNIFICANCE Despite hundreds of clinical trials, just one stem cell treatment has been approved for the U.S. market. Additional treatments nearing clinical acceptance use bone marrow mesenchymal stem cells for in-flammatory and immune-related conditions. This is because safety has been established over decades of testing, and cell transplants prolong life-saving organ and tissue grafts. In the present study, the intravenous delivery of mesenchymal stem cells enhanced the vision rescue from primary cell grafts into diseased retinae. This combined transplant strategy could improve functional outcomes for cell-based therapies, expand their utility, and expedite their clinical acceptance.

Most of current concepts for a visual prosthesis are based on neuronal electrical stimulation at different locations along the visual pathways within the central nervous system. The different designs of visual prostheses are named according to their locations (i.e., cortical, optic nerve, subretinal, and epiretinal). Visual loss caused by outer retinal degeneration in diseases such as retinitis pigmentosa or age-related macular degeneration can be reversed by electrical stimulation of the retina or the optic nerve (retinal or optic nerve prostheses, respectively). On the other hand, visual loss caused by inner or whole thickness retinal diseases, eye loss, optic nerve diseases (tumors, ischemia, inflammatory processes etc.), or diseases of the central nervous system (not including diseases of the primary and secondary visual cortices) can be reversed by a cortical visual prosthesis. The intent of this article is to provide an overview of current and future concepts of retinal and optic nerve prostheses. This article will begin with general considerations that are related to all or most of visual prostheses and then concentrate on the retinal and optic nerve designs. The authors believe that the field has grown beyond the scope of a single article so cortical prostheses will be described only because of their direct effect on the concept and technical development of the other prostheses, and this will be done in a more general and historic perspective..

In humans, the Crumbs homolog-1 (CRB1) gene is mutated in autosomal recessive Leber congenital amaurosis and early-onset retinitis pigmentosa. In mammals, the Crumbs family is composed of: CRB1, CRB2, CRB3A and CRB3B. Recently, we showed that removal of mouse Crb2 from retinal progenitor cells, and consequent removal from Müller glial and photoreceptor cells, results in severe and progressive retinal degeneration with concomitant loss of retinal function that mimics retinitis pigmentosa due to mutations in the CRB1 gene. Here, we studied the effects of cell-type-specific loss of CRB2 from the developing mouse retina using targeted conditional deletion of Crb2 in photoreceptors or Müller cells. We analyzed the consequences of targeted loss of CRB2 in the adult mouse retina using adeno-associated viral vectors encoding Cre recombinase and short hairpin RNA against Crb2. In vivo retinal imaging by means of optical coherence tomography on retinas lacking CRB2 in photoreceptors showed progressive thinning of the photoreceptor layer and cellular mislocalization. Electroretinogram recordings under scotopic conditions showed severe attenuation of the a-wave, confirming the degeneration of photoreceptors. Retinas lacking CRB2 in developing photoreceptors showed early onset of abnormal lamination, whereas retinas lacking CRB2 in developing Müller cells showed late onset retinal disorganization. Our data suggest that in the developing retina, CRB2 has redundant functions in Müller glial cells, while CRB2 has essential functions in photoreceptors. Our data suggest that short-term loss of CRB2 in adult mouse photoreceptors, but not in Müller glial cells, causes sporadic loss of adhesion between photoreceptors and Müller cells.

Magnetic fields have the potential to noninvasively direct and focus therapy to disease targets. External magnets can apply forces on drug-coated magnetic nanoparticles, or on living cells that contain particles, and can be used to manipulate them in vivo. Significant progress has been made in developing and testing safe and therapeutic magnetic constructs that can be manipulated by magnetic fields. However, we do not yet have the magnet systems that can then direct those constructs to the right places, in vivo, over human patient distances. We do not yet know where to put the external magnets, how to shape them, or when to turn them on and off to direct particles or magnetized cells-in blood, through tissue, and across barriers-to disease locations. In this article, we consider ear and eye disease targets. Ear and eye targets are too deep and complex to be targeted by a single external magnet, but they are shallow enough that a combination of magnets may be able to direct therapy t...

Retinitis pigmentosa results in blindness due to degeneration of photoreceptors, but spares other retinal cells, leading to the hope that expression of light-activated signaling proteins in the surviving cells could restore vision. We used a retinal G protein-coupled receptor, mGluR2, which we chemically engineered to respond to light. In retinal ganglion cells (RGCs) of blind rd1 mice, photoswitch-charged mGluR2 ("SNAG-mGluR2") evoked robust OFF responses to light, but not in wild-type retinas, revealing selectivity for RGCs that have lost photoreceptor input. SNAG-mGluR2 enabled animals to discriminate parallel from perpendicular lines and parallel lines at varying spacing. Simultaneous viral delivery of the inhibitory SNAG-mGluR2 and excitatory light-activated ionotropic glutamate receptor LiGluR yielded a distribution of expression ratios, restoration of ON, OFF and ON-OFF light responses and improved visual acuity. Thus, SNAG-mGluR2 restores patterned vision and combi...

Abstract. As previously reported in the literature, hyperbaric oxygen delivery seems to modify the natural course of retinitis pigmentosa. In order to evaluate these first encouraging data, 48 affected subjects were separately studied in two subgroups (cases and controls). All ...