Peripheral retinal breaks and retinal detachment

There is a broad assortment of vitreo-retinal abnormalities which can be encountered in the retinal periphery. They can often be challenging to both diagnose and treat. Both the American Academy of Ophthalmology (AAO) and the American Optometric Association (AOA) have developed clinical practice guidelines to assist the clinician in the identification and management of vitreo-retinal disease, peripheral retinal breaks and retinal detachment. These guidelines summarize the prevailing general opinion of the ophthalmic community regarding the diagnosis and treatment of peripheral retinal disease. This article presents a review of these guidelines along with a discussion of the similarities and differences of each and how they can be interpreted and applied clinically.     

Experimental retinal reattachment

In the feline model, retinal detachment initiates a cascade of changes that include photoreceptor-cell “deconstruction,” apoptotic death of some photoreceptors, neurite outgrowth from second-and third-order neurons, remodeling of photoreceptor synaptic terminals, and Müller-cell gliosis. We have previously shown that reattachment within 24 h halts or reverses many of these presumed detrimental changes. However, in patients with retinal detachments, reattachment cannot always be performed within this 24-h window. Moreover, recovery of vision following successful reattachment surgery in the macula is often imperfect. Here, we examine the ability of relatively long-term reattachment (28 d) to stop or reverse several cellular events that occur at 3 d of detachment. In contrast to earlier studies of reattachment, which focused on the regeneration of outer segments, we focus our attention here on other cellular events such as neuronal remodeling and gliosis. Some of these changes are reversed by reattachment, but reattachment itself appears to stimulate other changes that are not associated with detachment. The implications of these events for the return of vision are unknown, but they do indicate that simply reattaching the retina does not return the retina to its pre-detachment state within 28 d.     

Human retinal development: ultrastructure of the inner retinal layers

Studies of the developing human retina from 6.5 to 18 weeks' gestational age (16–156 mm) by light and electron microscopy are concerned with the morphogenesis of neuroblast cells, plexiform layers, and inner limiting membrane. The transient layer of Chievitz is formed posteriorly by 20 mm (7 weeks), inner plexiform by 48 mm (9 weeks), outer plexiform layer by 83 mm (12 weeks), identifiable cones by 83 mm, and rods by 120 mm (15 weeks). Mitotic activity continues posteriorly until 120 mm and was seen in inner layers of the retina until 103 mm (13 weeks). Outer neuroblastic differentiation is marked by diversification from a uniform cell population to one containing at least three cell types differing in their nuclear shape, chromatin pattern, and cytoplasmic characteristics. Differentiating ganglion cells accumulate polysomes, rough endoplasmic reticulum, Golgi complexes, microtubules, and dense bodies. Müller cell bodies in ganglion and inner nuclear layers extend processes between ganglion cells, and radial fibers, containing extensive smooth endoplasmic reticulum, to the vitreal surface. Synapses appear in the inner and outer plexiform layers by 83 mm (12 weeks), and by 120 mm (15 weeks) demonstrate a variety of conventional and ribbon forms similar to those found in the adult. Synaptogenesis therefore begins considerably before the development of photoreceptor outer segments.     

Building retinal connectomes

Understanding vertebrate vision depends on knowing, in part, the complete network graph of at least one representative retina. Acquiring such graphs is the business of synaptic connectomics, emerging as a practical technology due to improvements in electron imaging platform control, management software for large-scale datasets, and availability of data storage. The optimal strategy for building complete connectomes uses transmission electron imaging with 2nm or better resolution, molecular tags for cell identification, open-access data volumes for navigation, and annotation with open-source tools to build 3D cell libraries, complete network diagrams and connectivity databases. The first forays into retinal connectomics have shown that even nominally well-studied cells have much richer connection graphs than expected.     

Adrenergic retinal neurons

Summary Adrenergic retinal neurons have been studied in cynomolgus monkeys, cats, rabbits, guinea-pigs, rats, and mice with the fluorescence technique of Falck and Hillarp. With some species variations, three adrenergic fibre layers have been observed: an outer adrenergic fibre layer (all species) at the border between the inner nuclear and inner plexiform layers, a middle adrenergic fibre layer (rabbits, guinea-pigs, rats, and mice) in the middle of the inner plexiform layer, and an inner adrenergic fibre layer (rabbits) at the border between the inner plexiform layer and the ganglion cell layer. Similarly, three kinds of adrenergic nerve cells have been found: a somewhat heterogenous group of outer adrenergic cells (all species) situated in the innermost cell rows of the inner nuclear layer, eremite cells (rabbits, guinea-pigs, rats, and mice) within the inner plexiform layer and alloganglionic cells (all species) with a position and appearance resembling some of the ordinary non-adrenergic cells of the ganglion cell layer. All the adrenergic cells are star-shaped with slender branching processes running to the different adrenergic layers.The research reported in this document has been sponsored by the Air Force Office of Scientific Research under grant AF EOAR 66-14 through the European Office of Aerospace Research (OAR), United States Air Force, by the United States Public Health Service (grant no. NB 05236-02), by the Swedish Medical Research Council (grant no. B 66-320), and by the Faculty of Medicine, University of Lund, Sweden.     

Early changes in retinal 5'-nucleotidase activity in hereditary retinal degeneration

Activity of soluble cGMP phosphodiesterase (PDE) and of two membrane enzymes, 5'-nucleotidase and Na,K-ATPase, was studied in the developing retina of rats with inherited retinal degeneration. It was found that by day 10 of life, the content of 5'-nucleotidase in the afflicted rats was significantly reduced as compared with controls. This difference was unchanged throughout the subsequent animals' life. Na,K-ATPase activity in the afflicted and normal animals was the same. Within the first 45 days of life, PDE calculated with respect to the rhodopsin content was not different as regards both the afflicted and normal rats. When calculated with respect to protein, the changes in PDE corresponded with the reported data. The data obtained allowed a suggestion to be made that changes in 5'-nucleotidase in inherited retinal degeneration are disease-specific. They are accounted for by changes in the enzymes of nonphotoreceptor retinal membranes. The changes in PDE may be regarded as secondary, correlating with variation in the number of the photoreceptor membranes.     

Taurine protects against NMDA-induced retinal damage by reducing retinal oxidative stress

Amino Acids - This study aimed to evaluate effect of TAU on NMDA-induced changes in retinal redox status, retinal cell apoptosis and retinal morphology in Sprague–Dawley rats. Taurine was...     

In vitro differentiation of retinal pigment epithelium from adult retinal stem cells

One of the limitations in molecular and functional studies of the retinal pigment epithelium (RPE) has been the lack of an in vitro system retaining all the features of in vivo RPE cells. Retinal pigment epithelium cell lines do not show characteristics typical of a functional RPE, such as pigmentation and expression of specific markers. The present study was aimed at the development of culture conditions to differentiate, in vitro, retinal stem cells (RSC), derived from the adult ciliary body, into a functional RPE. Retinal stem cells were purified from murine eyes, grown as pigmented neurospheres and induced to differentiate into RPE on an extracellular matrix substrate using specific culture conditions. After 7-15 days of culture, pigmented cells with an epithelial morphology showed a polarized organization and a capacity for phagocytosis. We detected different stages of melanogenesis in cells at 7 days of differentiation, whereas RPE at 15 days contained only mature melanosomes. These data suggest that our protocol to differentiate RPE in vitro can provide a useful model for molecular and functional studies.     

Calcium and retinal function

We survey the primary roles of calcium in retinal function, including photoreceptor transduction, transmitter release by different classes of retinal neuron, calcium-mediated regulation of gap-junctional conductance, activation of certain voltage-gated channels for K⁺ and C1⁻, and modulation of postsynaptic potentials in retinal ganglion cells. We discuss three mechanisms for changing [Ca²⁺]_i, which include flux through voltage-gated calcium channels, through ligand-gated channels, and by release from stores. The neuromodulatory pathways affecting each of these routes of entry are considered. The many neuromodulatory mechanisms in which calcium is a player are described and their effects upon retinal function discussed.     

Development of retinal layers

A noticeable characteristic of nervous systems is the arrangement of synapses into distinct layers. Such laminae are fundamental for the spatial organisation of synaptic connections transmitting different kinds of information. A major example of this is the inner plexiform layer (IPL) of the vertebrate retina, which is subdivided into at least ten sublayers. Another noticeable characteristic of these retina layers is that neurons are displayed in the horizontal plane in a non-random array termed as mosaic patterning. Recent studies of vertebrate and invertebrate systems have identified molecules that mediate these interactions. Here, we review the last mechanisms and molecules mediating retinal layering.     

Taurine deficiency damages retinal neurones: cone photoreceptors and retinal ganglion cells

In 1970s, taurine deficiency was reported to induce photoreceptor degeneration in cats and rats. Recently, we found that taurine deficiency contributes to the retinal toxicity of vigabatrin, an antiepileptic drug. However, in this toxicity, retinal ganglion cells were degenerating in parallel to cone photoreceptors. The aim of this study was to re-assess a classic mouse model of taurine deficiency following a treatment with guanidoethane sulfonate (GES), a taurine transporter inhibitor to determine whether retinal ganglion cells are also affected. GES treatment induced a significant reduction in the taurine plasma levels and a lower weight increase. At the functional level, photopic electroretinograms were reduced indicating a dysfunction in the cone pathway. A change in the autofluorescence appearance of the eye fundus was explained on histological sections by an increased autofluorescence of the retinal pigment epithelium. Although the general morphology of the retina was not affected, cell damages were indicated by the general increase in glial fibrillary acidic protein expression. When cell quantification was achieved on retinal sections, the number of outer/inner segments of cone photoreceptors was reduced (20?%) as the number of retinal ganglion cells (19?%). An abnormal synaptic plasticity of rod bipolar cell dendrites was also observed in GES-treated mice. These results indicate that taurine deficiency can not only lead to photoreceptor degeneration but also to retinal ganglion cell loss. Cone photoreceptors and retinal ganglion cells appear as the most sensitive cells to taurine deficiency. These results may explain the recent therapeutic interest of taurine in retinal degenerative pathologies.     

Neuropeptides and retinal development

Different peptidergic systems have been investigated with some detail during retinal development, including substance P (SP), vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP) and somatostatin (SRIF). Concerning possible developmental actions of neuropeptides, VIP and PACAP exert protective and growth-promoting actions that may sustain retinal neurons during their development. In addition, the presence of transient SRIF expressing cells and recent observations in SRIF receptor knock out mice indicate variegated roles of this peptide in the development of the retina and of retinofugal projections. Finally, recent studies have shown that, in the developing rabbit retina, changes in the expression pattern of SP receptors are accompanied by modifications of SP physiological effects, indicating that retinal circuits where SP is involved are likely to function in a substantially different manner before the retina becomes involved in the processing of visual stimuli. SP neurotransmission in the immature retina may subserve developmental events, and SP is likely to represent an important developmental factor for the maturation of retinal neurons and circuitries.