Retina Research Papers - Academia.edu (original) (raw)

OBJECTIVE: To assess the impact of laser peripheral iridotomy (LPI) on forward-scatter of light and subjective visual symptoms and to identify LPI parameters influencing these phenomena. DESIGN: Cohort study derived from a randomized trial, using an external control group. PARTICIPANTS: Chinese subjects initially aged 50 or older and 70 years or younger with bilateral narrow angles undergoing LPI in 1 eye selected at random, and age- and gender-matched controls. METHODS: Eighteen months after laser, LPI-treated subjects underwent digital iris photography and photogrammetry to characterize the size and location of the LPI, Lens Opacity Classification System III cataract grading, and measurement of retinal straylight (C-Quant; OCULUS, Wetzlar, Germany) in the treated and untreated eyes and completed a visual symptoms questionnaire. Controls answered the questionnaire and underwent straylight measurement and (in a random one-sixth sample) cataract grading. MAIN OUTCOME MEASURES: Retina...

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- Ophthalmology, Solid state lasers, Visual acuity, Retina

The Alzheimer amyloid-β (Aβ) accumulates in several types of retinal degeneration and in Alzheimer disease (AD), but its source has been unclear. We detected the neuronal 695 amino acid form of Aβ-precursor protein (AβPP) in the normal retina and AβPP751 in the retinal pigment epithelium (RPE) and anterior eye tissues. Similar to the brain, αand β-secretases cleaved AβPP to soluble derivatives (sAPP) α or β and membrane-bound C-terminal fragments (CTF) α or β in the retina and RPE. Levels of sAPP were particularly high in the vitreous and low in aqueous humor revealing a molecular barrier for AβPP. In contrast, Aβ40 and Aβ42 levels were only 50% lower in the aqueous than the vitreous humor, indicating relatively barrier-free movement of Aβ. These studies demonstrated a relatively high yield of AβPP and Aβ 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 Aβ-related neurodegeneration in AD.

- by Rao Jagannatha
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- Cognitive Science, Biology, Medicine, Retinal Pigment Epithelium

All subjects were followed up for a minimum of 6 months and up to 2.7 years. Methods: The electronic stimulator and antenna of the implant were sutured onto the sclera using an encircling silicone band. Next, a pars plana vitrectomy was performed, and the electrode array and cable were introduced into the eye via a pars plana sclerotomy. The microelectrode array then was tacked to the epiretinal surface. Main Outcome Measures: The primary safety end points for the trial were the number, severity, and relation of adverse events. Principal performance end points were assessments of visual function as well as performance on orientation and mobility tasks. Results: Subjects performed statistically better with the system on versus off in the following tasks: object localization (96% of subjects), motion discrimination (57%), and discrimination of oriented gratings (23%). The best recorded visual acuity to date is 20/1260. Subjects' mean performance on orientation and mobility tasks was significantly better when the system was on versus off. Seventy percent of the patients did not have any serious adverse events (SAEs). The most common SAE reported was either conjunctival erosion or dehiscence over the extraocular implant and was treated successfully in all subjects except in one, who required explantation of the device without further complications. Conclusions: The long-term safety results of Second Sight's retinal prosthesis system are acceptable, and most subjects with profound visual loss perform better on visual tasks with system than without it.

- by ARTURO SANTOS
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- Ophthalmology, Blindness, Optical coherence tomography, Medicine

PURPOSE: To develop an optical coherence tomography (OCT) classification system that monitors the response of eyes treated with photodynamic therapy (PDT) with verteporfin for subfoveal choroidal neovascularization (CNV) from age-related... more

- by Carmen Puliafito
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- Optical coherence tomography, Porphyrins, Tomography, Photodynamic Therapy
- by Neil Ebenezer
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- Genetics, Human Genetics, Polymorphism, Complementary and Alternative Medicine
- by Enza Valente and +1
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- Pediatric Neurology, Retina, Neurosciences

Although biological cells are mostly transparent, they are phase objects that differ in shape and refractive index. Any image that is projected through layers of randomly oriented cells will normally be distorted by refraction, reflection, and scattering. Counterintuitively, the retina of the vertebrate eye is inverted with respect to its optical function and light must pass through several tissue layers before reaching the light-detecting photoreceptor cells.

- by Serguei Skatchkov and +1
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- Multidisciplinary, Lasers, Vertebrates, Retina

For successful restoration of visual function by retinal implant, a method for electrical stimulation should be devised so that the evoked activities of retinal ganglion cells (RGCs) should convey sufficient information on visual input. By observing RGC activities under different stimulation constraints, it may be possible to determine optimal pulse parameters, such as pulse rate, intensity, and duration, for faithful transmission of visual information. To test the feasibility of this approach, we analyzed RGC spike trains evoked by temporally patterned stimulation from retinal patches mounted on a planar multielectrode array. Assuming that the intensity of uniform visual input is transformed to amplitudes of pulse trains, we attempted to determine optimal methods for modulating the pulse amplitude so that the information essential for the perception of intensity variation is properly represented in RGC responses. RGC firing rates could be modulated to track the temporal pattern of pulse amplitude variations, which implies that pulse amplitude modulation is a plausible means to enable perception of temporal visual patterns by retinal implants. As expected, specific pulse amplitude modulation parameters were crucial for proper encoding of visual input. RGC firing rates increased monotonically according to the pulse amplitude in a defined pulse amplitude range (20-60 μA). The similarity between the RGC firing rate and the temporal pulse intensity pattern was highest when the pulse amplitude was modulated within this range. The optimal pulse rate range could be similarly determined.

- by Sang Ryu
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- Cognitive Science, Spike train analysis, Brain, Retina

Neuronal growth cones navigate over long distances along specific pathways to find their correct targets. The mechanisms and molecules that direct this pathfinding are the topics of this review. Growth cones appear to be guided by at... more

- by Corey Goodman
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- Cognitive Science, Molecular Biology, Science, Membrane Proteins

The poorly developed visual system of the electric catfish was studied with silver-degeneration methods. Retinal projections were entirely contralaterat to the hypothalamic optic nucleus, the lateral geniculate nucleus, the dorsomedial optic nucleus, the pretectal nuclei including the cortical nucleus, and the optic tectum. The small size and lack of differentiation of the visual system in the electric catfish suggest a relatively small role for this sensory system in this species.

- by S. Ebbesson
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- Biology, Medicine, Brain, Thalamus
- by F. Pricci
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- Electron Microscopy, Diabetes, Enzyme Inhibitors, Polymers
- by John Timoney
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- Mass Spectrometry, Biological Sciences, Antibodies, Retina

Refractory neovascular age-related macular degeneration (nAMD) is defined when intravitreal anti-vascular endothelial growth factor injection therapy results in poor response. Treatment of refractory patients determines the success or failure of treatment for nAMD. In this article, we present the definition and mechanism of refractory nAMD, and address various possible therapeutic approaches that can overcome refractoriness, such as switching drugs, increasing injection dosage or frequency, and combination therapy with photodynamic therapy or intravitreal steroid injection.

- by Irene Barbazetto
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- Ophthalmology, Porphyrins, Visual acuity, Macular Degeneration

Ahstract4hanges in arachidonic acid metabolism were studied in the optic nerve, the choriomtina, and in the vitreous following crush injury to the optic nerve of rats. Crush injury led to: (i) a 3.9-fold increase in optic nerve prostaglandin type Er in vitro production which peaked on day 5 and was followed by a gradual decline, but was still significantly higher than baseline levels by day 12; (ii) a twofold increase in the chorioretina prostaglandin type E, in vitro production which peaked on day 1, and resumed baseline levels by day 3; (iii) a 3.5-fold increase in vitreous prostaglandin type E, levels on day 1 which remained at 1.5-2 times higher than baseline levels for the rest of the study period (12 days). The findings indicate that the pattern of changes in prostaglandin type E, production by the optic nerve (consisting mostly of white matter) is different from that described for injured brain tissues. The prolonged accumulation of vitreal prostaglandin type E, in eyes with damaged optic nerve may lead to undesirable effects on the retina beyond those directly manifested in the retina by altered axonal flow in the injured optic nerve.

- by Michael Belkin
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- Neuroscience, Psychology, Inflammation, Optic Nerve

Arrestins are members of a superfamily of proteins that arrest the activity of G-protein coupled receptors. Mouse cone photoreceptors express two visual arrestins, Arr1 and Arr4 (Carr). We quantified their expression levels and subcellular distributions in mouse cones: total Arr1 was estimated to be in an ~ 6:1 ratio to cone opsin, about 50-fold higher than Arr4. Recordings from single cones of Arr1 −/− and Arr4 −/− mice establish that both proteins are competent to arrest the activity of photoactivated S-and M-cone opsins. Recordings from Arr1 −/− , Arr4 −/− double-knockout mice establish a requirement for at least one of the two visual arrestins for normal cone opsin inactivation at all flash intensities. These recordings also reveal low activity photoproducts of S-and M-opsins that are absent when Grk1 and an arrestin are co-expressed, but which decay 70-fold more rapidly than the comparable photoproducts of rhodopsin in rods.

- by Cheryl Craft
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- Cognitive Science, Electrophysiology, Confocal Microscopy, Mice
- by Tunde Peto
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- Global Health, Macular Degeneration, United States, Retina
- by Ildiko Toth
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- RNA, Immunohistochemistry, Western blotting, Biological Sciences

To investigate factors associated with reduced visual acuity during long-term follow-up of patients with idiopathic central serous chorioretinopathy (ICSC). Retrospective consecutive case series that included patients with ICSC who were younger than 50 years of age at the time of initial examination and were followed up for &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =3 years. The mean follow-up for 101 involved eyes of 61 patients was 9.8 years (median, 8.0 years). Eyes were stratified into two groups based on visual acuity at the final examination: Group 1, visual acuity of 2040 or better; and Group 2, visual acuity of worse than 2040. Findings identified as potential risk factors for reduced vision at the final follow-up examinations for Group 1 versus Group 2 included the following: macular retinal pigment epithelium atrophy (90.8% versus 96.0%, respectively; P = 0.68); persistent pigment epithelial detachment or persistent subretinal fluid (5.3% versus 28.0%, respectively; P = 0.004); recurrences (39.5% versus 68.0%, respectively; P = 0.020); laser treatment (28.9% versus 32.0%, respectively; P = 0.80); and submacular choroidal neovascularization (0.0 versus 8.0%, respectively; P = 0.059). Factors associated with reduced visual acuity during long-term follow-up of patients with ICSC included persistent pigment epithelial detachment and/or subretinal fluid, recurrences, and submacular choroidal neovascularization.

- by Harry Flynn
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- Visual acuity, Retina, Follow-up studies, Risk factors

We have initiated a genetic analysis of the zebrafish visual system to identify novel molecules involved in vertebrate retinal function. Zebrafish are highly visual; they have four types of cones as well as rod photoreceptors, making it possible to study both rod and cone-mediated visual responses. To identify visual mutants, optokinetic responses of mutagenized larvae are measured in a three-generation screen for recessive mutations. By measuring visual behavior our genetic screen has been targeted towards identifying mutants that do not have gross morphological abnormalities. The electroretinogram (ERG) of optokinetic-defective mutants is recorded and their retinas are examined histologically to localize defects to the retina. In this report, we summarize our screening results and ERG and histological analyses of the five morphologically normal mutants we have analyzed to date. Additionally, the more detailed characterization of a red-blind mutant that we have isolated is summariz...

- by Susan Brockerhoff
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- Vision, Mutation, Movement, Retina

We present a model of the mechanical and fluid forces associated with exudative retinal detachments where the retinal photoreceptor cells separate, typically from the underlying retinal pigment epithelium (RPE). By computing the total fluid volume flow arising from transretinal, vascular and RPE pump currents, we determine the conditions under which the subretinal fluid pressure exceeds the maximum yield stress holding

- by Tom Chou
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- Engineering, Retinal Pigment Epithelium, Cell separation, Biological Sciences

This research was conducted at the Institute for Cognitive Studies, Rutgers University, Newark, New Jersey, as part o f a doctoral dissertation. I wish to thank H. Wallach, D. Dinnerstein, and C. H. Harris for their contributions to this work. I musr also mention my deep indebtedness to Irvin Rock for the outstanding training and advice I have received from him.

- by Alan Gilchrist
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- Psychology, Cognitive Science, Visual perception, Depth Perception

Nr2e3 is a photoreceptor-specific nuclear receptor believed to play a role in photoreceptor development, differentiation, and survival. Much research has focused on the interaction of Nr2e3 with other transcription factors in determining the milieu of target gene expression in photoreceptors of the neonatal and adult retina. To investigate the downstream targets of Nr2e3 and thereby shed light on the functional pathways relevant to photoreceptor development and maintenance, expression profiling was performed on retinas from two different mouse knockout lines, one containing a targeted disruption of the Nr2e3 gene (Nr2e3À/À), the other containing a spontaneous null allele of the Nr2e3 locus (rd7). Using whole genome microarrays, mRNA expression profiles of retinas from the two mutant strains were compared to those of wildtype C57BL/6 mice over a time course that ranged from postnatal day (p) 2 to 6 months of age (p180). Additionally, expression profiling was performed on retinal explants treated with a putative NR2E3 agonist. The molecular profiling of Nr2e3À/À and rd7/rd7 retinas identified 281 putative Nr2e3dependent genes that were differentially expressed between wildtype and mutant retinas during at least one time point. Consistent with previous reports that Nr2e3 is necessary for the repression of conespecific genes, increased expression of cone-specific genes was observed in the mutant samples, thereby providing proof-of-concept for the microarray screen. Further annotation of these data sets revealed ten predominant functional classes involved in the Nr2e3-mediated development and/or maintenance of photoreceptors. Interestingly, differences in the expression of Nr2e3-dependent genes exhibited two distinct temporal patterns. One group of genes showed a sustained difference in expression as compared to wildtype over the entire time course of the study, whereas a second group showed only transient differences which were largest around p10. Comparison of gene expression changes in Nr2e3À/À and rd7/rd7 retinas with those uncovered by treating retinal explants with a putative NR2E3 agonist revealed four genes that were down-regulated in mutant retinas that lack Nr2e3 function but were up-regulated in agonist-treated explants. These results strongly suggest that the four genes may be direct targets of Nr2e3. Our identification of two sets of Nr2e3-regulated genes provides further evidence of a dual role for Nr2e3 in specification of photoreceptor fate during development as well as photoreceptor maintenance in the adult.

- by Konstantin Petrukhin
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- Gene expression, Nuclear Receptor, Microarray, Mice

The Virtual Retinal Display (VRD) is a new technology for creating visual images. It was developed at the Human Interface Technology Laboratory (HIT Lab) by Dr. Thomas A. Furness III. The VRD creates images by scanning low power laser light directly onto the retina. This special method results in images that are bright, high contrast and high resolution. In this paper, we describe how the VRD functions, the special consequences of its mechanism of action and potential medical applications of the VRD, including surgical displays and displays for people with low vision. A description of its safety analysis will also be included. In one set of tests we had a number of patients with partial loss of vision view images with the VRD. There were two groups of subjects: patients with macular degeneration, a degenerative disease of the retina and patients with keratoconus. Typical VRD images are on the order of 300 nanowatts. VRD images are also readily viewed superimposed on ambient room lig...

Joubert syndrome (JBTS) is a recessive ciliopathy in which a subset of affected individuals also have the skeletal dysplasia Jeune asphyxiating thoracic dystrophy (JATD). Here, we have identified biallelic truncating CSPP1 (centrosome and spindle pole associated protein 1) mutations in 19 JBTS-affected individuals, four of whom also have features of JATD. CSPP1 mutations explain~5% of JBTS in our cohort, and despite truncating mutations in all affected individuals, the range of phenotypic severity is broad. Morpholino knockdown of cspp1 in zebrafish caused phenotypes reported in other zebrafish models of JBTS (curved body shape, pronephric cysts, and cerebellar abnormalities) and reduced ciliary localization of Arl13b, further supporting loss of CSPP1 function as a cause of JBTS. Fibroblasts from affected individuals with CSPP1 mutations showed reduced numbers of primary cilia and/or short primary cilia, as well as reduced axonemal localization of ciliary proteins ARL13B and adenylyl cyclase III. In summary, CSPP1 mutations are a major cause of the Joubert-Jeune phenotype in humans; however, the mechanism by which these mutations lead to both JBTS and JATD remains unknown.

- by Zornitza Stark
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- Adolescent, Biological Sciences, Child, Mutation

Objective: To compare the effectiveness of low-luminance visual acuity (LLVA) and microperimetry as functional measures in early stages of age-related macular degeneration (AMD). Design: Prospective cross-sectional study. Participants: One hundred seventy-nine participants with a clinical spectrum of non-neovascular AMD and 26 control participants.

- by Robyn Guymer
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- Ophthalmology, Visual acuity, Prospective studies, Retina

The timecourse and scalp topography of interactions between neural responses to stimuli in different visual quadrants, straddling either the vertical or horizontal meridian, were studied in 15 subjects. Visual evoked potentials (VEPs) were recorded from 64 electrodes during a simple reaction time (RT) task. VEPs to single stimuli displayed in different quadrants were summed ('sum') and compared to the VEP response from simultaneous stimulation of the same two quadrants ('pair'). These responses would be equivalent if the neural responses to the single stimuli were independent. Divergence between the 'pair' and 'sum' VEPs indicates a neural response interaction. In each visual field, interactions occurred within 72 -86 ms post-stimulus over parieto-occipital brain regions. Independent of visual quadrant, RTs were faster for stimulus pairs than single stimuli. This replicates the redundant target effect (RTE) observed for bilateral stimulus pairs and generalizes the RTE to unilateral stimulus pairs. Using Miller's 'race' model inequality (Miller J. Divided attention: evidence for coactivation with redundant signals, Cognitive Psychology 1982;14:247-79), we found that probability summation could fully account for the RTE in each visual field. Although measurements from voltage waveforms replicated the observation of earlier peak P1 latencies for the 'pair' versus 'sum' comparison (Miniussi C, Girelli M, Marzi CA. Neural site of the redundant target effect: electrophysiological evidence. Journal of Cognitive Neuroscience 1998;10:216-30), this did not hold with measurements taken from second derivative (scalp current density) waveforms. Since interaction effects for bilateral stimulus pairs occurred within 86 ms and require interhemispheric transfer, transcallosal volleys must arrive within 86 ms, which is earlier than previously calculated. Interaction effects for bilateral conditions were delayed by :10 ms versus unilateral conditions, consistent with current estimates of interhemispheric transmission time. Interaction effects place an upper limit on the time required for neuronal ensembles to combine inputs from different quadrants of visual space ( : 72 ms for unilateral and : 82 ms for bilateral conditions).

- by Micah M. Murray
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- Psychology, Cognitive Psychology, Cognitive Science, Electrophysiology

With the introduction of spectral-domain optical coherence tomography (OCT), much larger image datasets are routinely acquired compared to what was possible using the previous generation of time-domain OCT. Thus, the need for 3-D segmentation methods for processing such data is becoming increasingly important. We report a graph-theoretic segmentation method for the simultaneous segmentation of multiple 3-D surfaces that is guaranteed to be optimal with respect to the cost function and that is directly applicable to the segmentation of 3-D spectral OCT image data. We present two extensions to the general layered graph segmentation method: the ability to incorporate varying feasibility constraints and the ability to incorporate true regional information. Appropriate feasibility constraints and cost functions were learned from a training set of 13 spectral-domain OCT images from 13 subjects. After training, our approach was tested on a test set of 28 images from 14 subjects. An overall mean unsigned border positioning error of 5 69 2 41 m was achieved when segmenting seven surfaces (six layers) and using the average of the manual tracings of two ophthalmologists as the reference standard. This result is very comparable to the measured interobserver variability of 5 71 1 98 m.

- by Stephen Russell
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- Engineering, Algorithms, Medical Imaging, Optical coherence tomography

We have measured the spread of contrast adaptation across the dimension of spatial frequency. Threshold elevation was tightly tuned to the adapting spatial frequency but became much broader as test contrast was increased. This means that, for a given test frequency, there arc some frequencies which do not raise threshold but do result in a loss of perceived contrast. The contrast dependence, retinal specificity and interocular transfer of adaptation effects elicited from sameand remote-frequency adaptation were compared. While we were able to show some distinct differences between threshold and suprathreshold tests, we were unable to demonstrate any reliable differences in the retinal specificity and interocular transfer between same-and remotefrequency adaptation.

- by Robert Snowden
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- Psychophysics, Adaptation, Vision, Retina

We investigated the effect of depleting membrane docosahexaenoic acid (DHA, 22 : 6n-3) content through dietary deprivation of n-3 fatty acids on the susceptibility of the photoreceptors and pigment epithelium cells to acute light-induced changes. Male Sprague-Dawley rats were raised throughout gestation, lactation and up to the age of 8 weeks on semi-purified diets containing either &lower oil (SFO, n-3 deficient diet) or soybean oil (SO) as the sole source of lipids. A third group was switched at weaning from safflower oil to soybean oil (SFO/SO). Rats were maintained on a 12 hr/12 hr light/dark cycle in which the light level at the front of the cages was S-10 lx. Light damage was produced by exposing darkadapted animals to diffuse white fluorescent light of 700-800 Ix for 30 min followed by 90 min of darkness. In order to study recovery from light damage, additional groups of SF0 and SO rats were returned to dim cyclic light for 27 hr following bright light exposure. DHA content in retinal phosphatidylethanolamine and phosphatidylcholine was 65-75 % lower in rats fed SF0 than in rats fed SO. The decrease was compensated for by an increase in 22 : Sn-6. the total content of polyunsaturated fatty acids (PUFA) being similar iu both the SF0 and SO groups. The SFO/SO rats had DHA levels similar to SO animals, but 22 : Sn-6 remained elevated resulting in a slightly higher level of total PUFA. Severe rod outer segment (ROS) membrane disruptions were seen following bright light exposure in rats on the SO and SFO/SO diets. The appearance of these disruptions did not change significantly during more than 24 hr in dim cyclic light. In contrast, there were virtually no acute ROS lesions in the SF0 group. Furthermore, there was a strong light-elicited disk-shedding response in the SO rats but not in the other two groups. The pigment epithelium of the DHA deficient retinas showed a significantly greater accumulation of large lipid droplets in the dark-adapted state. Notably, whole retina rhodopsin levels were 15% higher in the SF0 than in the SO group. These results indicate that depletion of retinal DHA reduces the susceptibility of the rod outer segments to acute light damage and at the same time may alter visual pigment photochemistry and other photoreceptor and pigment epithelium functions.

- by Charlotte Remé
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- Electron Microscopy, Omega-3 fatty acids, Retina, Light

Two objects that project the same visual angle on the retina can appear to occupy very different proportions of the visual field if they are perceived to be at different distances. What happens to the retinotopic map in primary visual cortex (V1) during the perception of these size illusions? Here we show, using functional magnetic resonance imaging (fMRI), that the retinotopic representation of an object changes in accordance with its perceived angular size. A distant object that appears to occupy a larger portion of the visual field activates a larger area in V1 than an object of equal angular size that is perceived to be closer and smaller. These results demonstrate that the retinal size of an object and the depth information in a scene are combined early in the human visual system.

- by D. Kersten
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- Cognitive Science, Visual perception, Magnetic Resonance Imaging, Space perception

Canine generalised progressive retinal atrophy (gPRA) is a large and ever-increasing collection of naturally occurring, heterogeneous, progressive disorders. Most are inherited in an autoso-ma1 recessive manner and new, breed-specific forms continue to be described. The gPRAs cause photoreceptor cell death and subsequent retinal degeneration, culminating in blindness. In humans, similar inherited retinal dystrophies are recognised as retinitis pigmentosa and macular dystrophy. Molecular biological studies have revealed disease-causing mutations in several genes in humans and also in mice with retinal dystrophies. Recently, molecular genetic techniques have identified the cause of one form of gPRA in Irish setters while important candidate genes have been investigated in other breeds. Identification of mutations responsible for different forms of gPRA allows carrier and predegenerate animals to be detected using DNA-based tests. Such genetic tests will greatly facilitate the eradication of these diseases in different breeds.

- by D. Sargan
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- Dogs, Mice, Retinitis pigmentosa, Retina

Non-arteritic anterior ischemic optic neuropathy is caused by a transient optic nerve ischemia and results in permanent vision loss. Currently, there is no effective treatment for this ischemic optic nerve injury. This study characterized the duration and extent of ischemia induced after a coagulopathy injury to the optic nerve of adult rats. Acute ischemia was induced in adult rats by intravenous injection of Rose Bengal dye, followed by argon green laser treatment of the vessels at the optic disc. Rats were assessed in the short-term for hypoxyprobe-1 binding and expression of hypoxia inducible factor-1α (HIF-1 α) and fractin, markers of neuronal injury. Five months after injury, optic axon number was quantified. The coagulopathy injury resulted in short-term hypoxia in the optic nerve and retina. Tissues were hypoxic within 15 min of the coagulopathy injury, but normoxic by 24 h as measured by hypoxyprobe-1 staining. Both HIF-1α and fractin were upregulated in ganglion cells variably across the retina. Five months after the ischemic injury, there was a 71% reduction in optic axon number compared to controls. It is critical to have a reproducible and relevant method for producing transient hypoxia in order to test therapeutic strategies for rescuing injured neurons. The coagulopathy induced in this study resulted in a reproducible and transient ischemic optic nerve injury and long-term axonal loss. This ischemia shows similar, although not identical, morphological and physiological changes to those seen in the human eye after optic nerve ischemia. We are currently testing therapeutic strategies to protect ganglion cells from degeneration after this ischemic injury.

- by Linda McLoon
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- Cognitive Science, Survival Analysis, Hypoxia, Brain
- by Sacha Reichman
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- Tissue Engineering, Induced Pluripotent Stem Cells (I Psc), Retina
- by Hermann Steller
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- Cognitive Science, Stem Cells, DNA replication, Drosophila melanogaster

Spatial correlation was observed between the localization of laminin-1 at the inner limiting membrane (ILM) and extensive Muller glial process arborization in the same area, as demonstrated by immunolabeling of Muller glial processes and laminin-1 in rat retinae in situ. To test if this spatial correlation is due to a functional relationship, we investigated the impact of laminin-1 on the motility of cultured primary rat and mouse retinal Muller glial cells by statistical analysis of computer-controlled videomicroscopic time-lapse images. We demonstrate that laminin-1 increases motility and path-searching activity of Muller cells in vitro and it also enhances the cells' process formation/withdrawal dynamism. The increase in path-searching activity and cell process dynamism indicates that there is a functional relationship between laminin-1 and Muller glial cells presumably involving signaling towards the cytoskeleton. We hypothesize that laminin-1 is involved in process arborization of Muller cells at the vitread border of the retina resulting in the formation of the functional barrier made up of Muller glial endfeet.

- by V. Jancsik
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- Immunohistochemistry, Video microscopy, Mice, Retina

Akstraet--A pre-requisite to understanding the physiological mechanisms of action of melatonin is the identification of the target sites where the hormone acts. The radioligand 2-[t25I]iodomelatonin has been used extensively to localize binding sites in both the brain and peripheral tissues. In general these binding sites have been found to be high affinity, with Kd in the low picomolar range, and selective for structural analogues of melatonin. Also the affinity of these sites can generally be modulated by guanine nucleotides, consistent with the notion that they are putative G-protein coupled receptors. However, only a few studies have demonstrated that these putative receptors mediate biochemical and cellular responses. In the pars tuberalis (PT) and pars distalis (PD) of the pituitary, the amphibian melanophore and vertebrate retina, evidence indicates that melatonin acts to inhibit intracellular cyclic AMP through a G-protein coupled mechanism, demonstrating that this is a common signal transduction pathway for many melatonin receptors. However in the pars distalis the inhibition of calcium influx and membrane potential are also important mediators of melatonin effects. How many different forms or states of the melatonin receptor exist is unknown, but clearly the identification of the structure of the melatonin receptor(s) and its ability to interact with different G-proteins and signal transduction pathways are quintessential to our understanding of the physiological mechanisms of action of melatonin. In parallel the recent development of new melatonin analogues will greatly aid our understanding of the pharmacology of the melatonin receptor both in terms of the development of potent melatonin receptor antagonists and for the definition of receptor sub-types.

- by Peter Morgan
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- Neurochemistry, Melatonin, Retina, Pituitary Gland

Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in the U.S. The vision-threatening processes of neuroglial and vascular dysfunction in DR occur in concert, driven by hyperglycemia and propelled by a pathway of inflammation, ischemia, vasodegeneration, and breakdown of the blood retinal barrier. Currently, no therapies exist for normalizing the vasculature in DR. Here, we show that a single intravitreal dose of adeno-associated virus serotype 2 encoding a more stable, soluble, and potent form of angiopoietin 1 (AAV2.COMP-Ang1) can ameliorate the structural and functional hallmarks of DR in Ins2Akita mice, with sustained effects observed through six months. In early DR, AAV2.COMP-Ang1 restored leukocyte-endothelial interaction, retinal oxygenation, vascular density, vascular marker expression, vessel permeability, retinal thickness, inner retinal cellularity, and retinal neurophysiological response to levels comparable with nondiabetic control...

- by Kortnie Walker
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- Diabetes, Medicine, Protein Stability, Diabetic Retinopathy
- by Carla Podella
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- Nutrition and Dietetics, Pharmacogenomics, Epigenetics, Medicine

Background: Age-related macular degeneration (AMD) is the leading cause of central vision loss in older adults. Anti-retinal autoantibodies (AAbs) have been found in individuals with AMD. The goal of the study was to determine the AAb specificity in different stages of AMD, and determine whether there is a prevalent AAb signature. Methods: Sera of 134 participants in the Age-related Eye Disease Study were analyzed for anti-retinal AAbs by western blotting. The subjects were classified by diagnostic subgroups based upon their clinical classification: No AMD, Intermediate AMD, and Late AMD-geographic atrophy (GA) and Late AMD-neovascular (NV). Results: The presence of anti-retinal AAb was detected in 58% patients with Intermediate and Late AMD, and 54% of those with no AMD. AAbs bound to fifteen different retinal antigens. Most individuals had 1 specific AAbs (67%), with the remainder having 2 to 4 different AAbs. Over 40% of patients with Intermediate AMD, and 46% of those with GA had anti-enolase AAbs, compared with 29% of individuals with NV and 29% with no AMD. Different AAbs signatures related to NV as compared to GA and/or Intermediate AMD were distinguished. Anti-40-kDa (10%) and 42-kDa (16%) autoantibodies were associated with Intermediate AMD, while anti-30-kDa AAbs (23%) were primarily present in GA. Anti-32-kDa (12%), 35-kDa (21%), and 60-kDa (8%) AAbs were more frequent in NV AMD. Conclusions: A unique AAb pattern for each of the disease subgroups was present when AMD progressed from the intermediate to the late forms of severity. Differences in the frequency of specific AAbs between AMD subgroups suggested that they may participate in pathogenicity of AMD. Further studies are necessary to confirm these observations in the larger cohort and individual AMD patients over time.

- by Frederick Ferris
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- Western blotting, Smoking, Retina, Arthritis

BACKGROUND: Ciliopathies are an extensive group of autosomal recessive or X-linked disorders with considerable genetic and clinical overlap, which collectively share multiple organ involvement and may result in lethal or viable phenotypes. In large numbers of cases the genetic defect remains yet to be determined. The aim of this study is to describe the mutational frequency and phenotypic spectrum of the CEP120 gene. METHODS: Exome sequencing was performed in 145 patients with Joubert syndrome (JS), including 15 children with oral-facial-digital syndrome type VI (OFDVI) and 21 Meckel syndrome (MKS) fetuses. Moreover, exome sequencing was performed in one fetus with tectocerebellar dysraphia with occipital encephalocele (TCDOE), molar tooth sign and additional skeletal abnormalities. As a parallel study, 346 probands with a phenotype consistent with JS or related ciliopathies underwent nextgeneration sequencing-based targeted sequencing of 120 previously described and candidate ciliopathy genes. RESULTS: We present six probands carrying nine distinct mutations (of which eight are novel) in the CEP120 gene, previously found mutated only in Jeune asphyxiating thoracic dystrophy (JATD). The CEP120-associated phenotype ranges from mild classical JS in four patients to more severe conditions in two fetuses, with overlapping features of distinct ciliopathies that include TCDOE, MKS, JATD and OFD syndromes. No obvious correlation is evident between the type or location of identified mutations and the ciliopathy phenotype. CONCLUSION: Our findings broaden the spectrum of phenotypes caused by CEP120 mutations that account for nearly 1% of patients with JS as well as for more complex ciliopathy phenotypes. The lack of clear genotype-phenotype correlation highlights the relevance of comprehensive genetic analyses in the diagnostics of ciliopathies.

- by Joachim Van Keirsbilck
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- Medical Genetics, Biological Sciences, Child, Cerebellum

Introduction A program involving three operations, 1 to reattach most of the retina under oil, 2 to reattach the remaining retina by planned delayed relaxing retinectomy (PDRR) and 3 to remove silicone oil was tested Methods Review of electronic patient records of patients receiving PDRR for PVR. Primary end point reattached retina without silicone oil. Results 87 patients had PVR, 27 received PDRR mean age 66.6 years, mean follow up 2.3 years. Ten had grade B PVR, 8 CP1-CP6 and 7 CA2-CA6. 24 patients (89%) achieved a reattached retina without silicone oil. LogMar visions were mean 1.41 (SD 0.67) at presentation and 1.21 (SD 0.58) at final follow up. 4 patients suffered glaucoma and one scleromalacia. The overall success rate for all patients with PVR was 85% reattached retina without oil tamponade. Conclusions PDRR contributes to a high chance of reattached retina and oil removal in PVR.

- by Tom Williamson
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- Treatment Outcome, Visual acuity, Cryotherapy, Retina

Accommodation stimulus-response function (ASRF) and its relationship to retinal image quality were investigated using a modified wavefront sensor. Ten subjects were presented with six vergence stimuli between 0.17 D and 5 D. For each vergence distance, ocular wavefronts and subjective visual acuity were measured. Wavefronts were analysed for a fixed 3-mm pupil diameter and for natural pupil sizes. Visual Strehl ratio computed in the frequency domain (VSOTF) and retinal images were calculated for each condition tested. Subjective visual acuity was significantly improved at intermediate vergence distances (1 D and 2 D; p < 0.01), and only decreased significantly at 5 D compared with 0.17 D (p < 0.05). VSOTF magnitude was associated with subjective visual acuity and VSOTF peak location correlated with accommodation error. Apparent accommodation errors due to spherical aberration were highly correlated with accommodation lead and lag for natural pupils (R 2 = 0.80) but not for fixed 3-mm pupils (R 2 < 0.00). The combination of higher-order aberrations and accommodation errors improved retinal image quality compared with accommodation errors or higher order aberrations alone. Pupil size and higher order aberrations play an important role in the ASRF.

- by Tobias Buehren
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- Binocular vision, Visual acuity, Accommodation, Vision
- by Dhananjay Shukla
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- Immunology, Retina, Clinical Sciences, Eye

Citation: Aboshiha J, Kumaran N, Kalitzeos A, Hogg C, Rubin G, Michaelides M. A quantitative and qualitative exploration of photoaversion in achromatopsia. Invest Ophthalmol PURPOSE. Photoaversion (PA) is a disabling and ubiquitous feature of achromatopsia (ACHM). We aimed to help define the characteristics of this important symptom, and present the first published assessment of its impact on patients' lives, as well as quantitative and qualitative PA assessments.

- by Chris Hogg
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- Finance, Qualitative methodology, Banking, Gender

Purpose: To assess the impact of phacoemulsification performed one week before pars plana vitrectomy versus combined phacovitrectomy on postoperative anterior segment status and final functional and anatomical outcomes in phakic patients... more

- by Stefano Baiocchi and +1
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- Retina, Optometry and Ophthalmology

Autoradiographic analysis of the primary retinal projections in the thornback guitarfish reveals both contralateral and ipsilateral projections to diencephalic, pretectal, and tegmental nuclei and the optic tectum. A total of 12... more

- by John Wathey
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- Psychology, Cognitive Science, Brain Mapping, Optic Nerve