Types Of Retinal Degeneration Research Articles

Oxysterols and retinal degeneration.

Retinal degeneration, characterised by the progressive death of retinal neurons, is the most common cause of visual impairment. Oxysterols are the cholesterol derivatives produced via enzymatic and/or free radical oxidation that regulate cholesterol homeostasis in the retina. Preclinical and clinical studies have suggested a connection between oxysterols and retinal degeneration. Here, we summarise early and recent work related to retina oxysterol-producing enzymes and the distribution of oxysterols in the retina. We examine the impact of loss of oxysterol-producing enzymes on retinal pathology and explore the molecular mechanisms associated with the toxic or protective roles of individual oxysterols in different types of retinal degeneration. We conclude that increased efforts to better understand the oxysterol-associated pathophysiology will help in the development of effective retinal degeneration therapies. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.

Release of Retinal Extracellular Vesicles in aModel of Retinitis Pigmentosa.

Extracellular vesicles (EVs) are membranous structures released by cells, including those of the retinal pigment epithelium (RPE) and photoreceptors. The cargo of EVs includes genetic material and proteins, making these vesicles essential in cell communication. Among the genetic materials, we find a large number of microRNAs (miRNAs), small chains of noncoding RNA. In the case of EVs from the retina, changes have also been observed in the number and cargo of EVs.Our group confirmed that damaged RPE cells in vitro release a greater number of EVs with a higher pro-angiogenic factor (VEGFR-1 and VEGFR-2) than control non-damaged cells, thus increasing neovascularization in endothelial cell cultures. This indicates that something similar could happen in patients suffering from some types of retinal degeneration that occur with angiogenesis, such as wet AMD or RD.Here, we investigated the role of EVs in photoreceptor degeneration, and we report for the first time on CD9 and CD81, closely related tetraspanins, in wild-type and rd1 retinae. Our study demonstrates the involvement of EVs in the process of inherited photoreceptor degeneration in a PDE6 mutation.

Long-term anesthetic protocol in rats: feasibility in electrophysiology studies in visual prosthesis.

Electrical stimulation of excitable cells provides therapeutic benefits for a variety of medical conditions, including restoration of partial vision to those blinded via some types of retinal degeneration. To improve visual percepts elicited by the current technology, researchers are conducting acute electrophysiology experiments, mainly in cats. However, the rat can provide a model of a range of retinal diseases and possesses a sufficiently large eye to be used in this field. This article presents a long-term anesthetic protocol to enable electrophysiology experiments to further the development of visual prostheses. Six Long-Evans rats (aged between 14 and 16 weeks) were included in this study. Surgical anesthesia was maintained for more than 15 h by combining constant intravenous infusion of ketamine (24.0-34.5 mg/kg/h), xylazine (0.9-1.2 mg/kg/h), and inhaled isoflurane in oxygen (<0.5%). Overall heart rate, respiratory rate, and body temperature remained between 187-233 beats/min, 45-58 breaths/min, and 36-38 °C, respectively. Neural responses to 200-ms light pulses were recorded from the superior colliculus using a 32-channel neural probe at the beginning and before termination of the experiment. Robust responses were recorded from distinct functional types of retinal pathways. In addition, a platinum electrode was implanted in the retrobulbar space. The retina was electrically stimulated, and the activation threshold was determined to be 5.24 ± 0.24 μC/cm2 . This protocol may be used not only in the field of visual prosthesis research, but in other research areas requiring longer term acute experiments.

Simulation Study of an Ultrasound Retinal Prosthesis With a Novel Contact-Lens Array for Noninvasive Retinal Stimulation.

Millions of people around the world suffer from varying degrees of vision loss (including complete blindness) because of retinal degenerative diseases. Artificial retinal prosthesis, which is usually based on electrical neurostimulation, is the most advanced technology for different types of retinal degeneration. However, this technology involves placing a device into the eyeball, and such a highly invasive procedure is inevitably highly risk and expensive. Ultrasound has been demonstrated to be a promising technology for noninvasive neurostimulation, making it possible to stimulate the retina and induce action potentials similar to those elicited by light stimulation. However, the technology of ultrasound retinal stimulation still requires considerable developments before it could be applied clinically. This paper proposes a novel contact-lens array transducer for use in an ultrasound retinal prosthesis (USRP). The transducer was designed in the shape of a contact lens so as to facilitate acoustic coupling with the eye liquid. The key parameters of the ultrasound transducer were simulated, and results are presented that indicate the achievement of 2-D pattern generation and that the proposed contact-lens array is suitable for multiple-focus neurostimulation, and can be used in a USRP.

Differential accumulation of secreted AbetaPP metabolites in ocular fluids.

Amyloid-beta (Abeta) accumulates in several types of retinal degeneration and in Alzheimer's disease (AD), but its source has been unclear. We detected the neuronal 695 amino acid form of amyloid-beta protein precursor (AbetaPP) in the normal retina and AbetaPP751 in the retinal pigment epithelium (RPE) and anterior eye tissues. Similar to the brain, alpha- and beta-secretases cleaved AbetaPP to soluble derivatives (sAbetaPP) alpha or beta and membrane-bound C-terminal fragments alpha or beta in the retina and RPE. Levels of sAbetaPP were particularly high in the vitreous and low in aqueous humor revealing a molecular barrier for AbetaPP. In contrast, Abeta40 and Abeta42 levels were only 50% lower in the aqueous than the vitreous humor, indicating relatively barrier-free movement of Abeta. These studies demonstrated a relatively high yield of AbetaPP and Abeta in the ocular fluids, which may serve as a trackable marker for AD. In addition, failure of free clearance from the eye may trigger retina degeneration in a manner similar to Abeta-related neurodegeneration in AD.

Stem cell biology and cell transplantation therapy in the retina

Embryonic stem (ES) cells, which are derived from the inner cell mass of mammalian blastocyst stage embryos, have the ability to differentiate into any cell type in the body and to grow indefinitely while maintaining pluripotency. During development, cells undergo progressive and irreversible differentiation into specialized adult cell types. Remarkably, in spite of this restriction in potential, adult somatic cells can be reprogrammed and returned to the naive state of pluripotency found in the early embryo simply by forcing expression of a defined set of transcription factors. These induced pluripotent stem (iPS) cells are molecularly and functionally equivalent to ES cells and provide powerful in vitro models for development, disease, and drug screening, as well as material for cell replacement therapy. Since functional impairment results from cell loss in most central nervous system (CNS) diseases, recovery of lost cells In addition to donor cell or tissue preparation, manipulation of the host conditions is essential for successful transplantation. Diseased host tissue may exhibit pathological conditions that differ from normal physiological conditions. For instance, inflammation affects the survival, synapse formation, and neural activity of transplanted cells, and except in cases of autotransplantation, immune rejection occurs following cell transplantation. The optimal time windows for photoreceptor transplantation should be determined for every type of retinal degeneration. A better understanding of the pathological host conditions, including immune responses, will be essential for regeneration of retinal function. Optimization of pharmacological drugs and transplantation materials are therefore crucial for successful transplantation.

Calpain activity in retinal degeneration

Retinal degenerations such as retinitis pigmentosa (RP) or glaucoma are a major cause of blindness in humans. Understanding the mechanisms underlying the various types of retinal degeneration is a pre-requisite for the development of rational therapies for these diseases. Activation of the calcium dependent protease, calpain, has been suggested to play an important role in cell death in various neuronal tissues including the retina. Improved detection and analysis of calpain activity during degenerative processes is likely to expand the list of pathological conditions with calpain involvement. We give a short overview of the methods available for the detection of calpain activity, and briefly discuss properties of calpain inhibitors. We then discuss the role of calpains in different cell death mechanisms and review existing work on retinal degeneration and the possible involvement of calpains therein. The implication of calpains in retinal cell death raises the possibility to use calpain inhibitors to prevent or delay retinal degeneration.

Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-1 in the Retinal Pigment Epithelium and Interphotoreceptor Matrix: Vectorial Secretion and Regulation

Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) play an essential role in both normal and pathological extracellular matrix degradation, and a TIMP has been associated with at least one type of retinal degeneration. We have studied expression of MMP-2 and TIMP-1 by zymography, immunocytochemistry, and immunoblotting in the retinal pigment epithelium (RPE) from normal, aged and diseased retinas. MMPs and TIMPs were found in the rat RPE, interphotoreceptor matrix (IPM), and in media conditioned by human and rat RPE in culture. In other polarized cells, MMPs and TIMP-2 are secreted vectorially towards the basal lamina. In the RPE, however, MMP-2 and TIMP-1 were secreted preferentially from the apical surface, the surface bordering the IPM. These findings provide new evidence that MMPs and TIMPs could play a role in the turnover of IPM components.Cell homogenates and conditioned media from RPE isolated from mutant Royal College of Surgeons (RCS) rats with inherited retinal dystrophy had similar amounts of MMP-2 and TIMP-1 as those from congenic control rats. The secretion of MMP-2 and TIMP-1 from RPE cell cultures isolated from young and aged human donors varied widely. However, with increasing cell passage number, secretion of MMPs and TIMPs from human RPE increased dramatically. Also, growing human RPE on bovine corneal endothelial cell-generated extracellular matrix instead of plastic reduced the secretion of both MMPs and TIMPs. These data suggest that the integrity of Bruch's membrane may serve to regulate RPE functions in MMP and TIMP secretion and that extracellular matrices contain signals that regulate MMP and TIMP synthesis and/or secretion by the RPE.

The management of labor in high myopic patients

The routine in our department for years used to be: prevention of bearing down during the end of the 2nd stage of labor in high myopic parturients, by forceps delivery, with the assumption that this will prevent increased intraocular pressure—thus preventing deterioration or increased damage to the eyes. The goal of this study was to challenge our theory and thus we decided to re-evaluate this approach. Various obstetrical data were recorded in 50 women with myopia from 4.5 to 15.0 diopters who were admitted in labor to our department. Fundus examination was performed in all of them before and after delivery. Various types of retinal degeneration and retinal breaks were observed in most of them at their arrival but no deterioration of these retinal defects was observed in any of the cases at the later examination. In view of our results, it is recommended to let high myopic patients deliver spontaneously.

Electron microscopic studies on celestial goldfish retina—A possible new type of retinal degeneration in experimental animals

The celestial goldfish (Carassius auratus) is one of the varieties of telescopic-eye goldfish, and a product of artificial selection. Their eyes are soft and telescopic anterior to dorsal. Abnormally thin retinas of celestial goldfish have only a small number of photoreceptor cells, and show various stages of retinal degeneration. The outer segments are short and markedly disorganized or often missing. Macrophages lies close to the outer or inner segments in single or clumped states, and sometimes replace the photoreceptor layer and/or the pigment epithelial layer. In a highly degenerated retina, the macrophages migrate to the inner layers or to around retinal vessels on the vitreous surface of the retina. The morphology of the celestial goldfish retina is regionally highly variable and also varies greatly between individuals. It is possible that this is a new type of primary retinal degeneration in experimental animals, although accompanying ocular enlargement.

A selected review of current retinal research and study.

The present paper reviews recent studies of retinal pathology from the American and British Journals of Ophthalmology during a one-year period (1973-1974). Selection is on the basis of potential value to clinical optometrists. Certain underlying factors in several types of retinal degeneration are first discussed, followed by characteristics of diabetic maculopathy and of other types of macular degeneration including that due to aging. Some material is presented on retinopathies related to sickle cell traits, to viral and worm infections, and to injury. Following a review of certain recent studies of retinoschisis, retinoblastoma, and retrolental fibroplasia, a concluding section deals with retinal detachments and breaks.

Two types of retinal degeneration in cerebellar mutant mice.

HUMAN retinitis pigmentosa represents a class of diseases, the principal characteristic of which is the slow and progressive degeneration of photoreceptor cells. In several human neurological syndromes, photoreceptor degeneration accompanies cerebellar ataxia, deafness, mental retardation or other abnormalities. Some examples of such syndromes are BattenSpielmeyer–Vogt disease, Refsum's disease, Laurence–Moon Biedl syndrome, Bassen–Kornzweig disease, Usher's syndrome and several of the mucopolysaccharidoses1–4. As far as we know laboratory animals with neurological syndromes that include photoreceptor degeneration have not been available.

RETINAL DEGENERATION IN MACULAR REGION WITHOUT CEREBRAL SYMPTOMS

The types of retinal degeneration in the macular region are based on differences in the ophthalmoscopic picture and also on the presence or absence of associated mental involvement. The following six cases are reported as examples of the macular type of maculocerebral degeneration (Oatman) or of progressive family degeneration in the macular region without psychic disturbance (Stargardt). REPORT OF CASES Case1.—W. F., a boy, aged 11, seen on March 24, 1915, said that his sight had been failing for one year. There was no consanguinity, familial history or hemeralopia. His previous illnesses were meningitis (?), measles, mumps and cyclical albuminuria. He was a healthy-appearing, intelligent boy. Vision with correcting glasses was 20/70. The field showed a central scotoma. The optic nerve and vessels were normal. In both macular regions, there were superficial choroidal changes consisting of depigmentation and irregular pigment hypertrophy. Surrounding this area, there were many small blurred