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Retina (Philadelphia, Pa.) Feb 2018To quantify retinal capillary density and determine its correlation with visual acuity in patients with birdshot chorioretinopathy (BCR).
PURPOSE
To quantify retinal capillary density and determine its correlation with visual acuity in patients with birdshot chorioretinopathy (BCR).
METHODS
Patients with BCR and age-matched controls were imaged using a commercially available spectral domain optical coherence tomography angiography system (RTVue- XR Avanti; Optovue, Inc). We used the integrated software of the optical coherence tomography angiography device to analyze the foveal avascular zone area and the capillary density in the full retina as well as in the superficial capillary plexus and deep capillary plexus. We assessed the correlation between these parameters and visual acuity.
RESULTS
Seventy-four eyes of 42 study participants (37 eyes of 21 BCR and 37 eyes of 21 healthy subjects) were included in this observational cross-sectional study. Capillary density of the full retina, superficial capillary plexus, and deep capillary plexus were significantly decreased in BCR compared with the healthy control group (P < 0.01). Visual acuity in patients with BCR was significantly associated with the capillary density of the superficial capillary plexus, deep capillary plexus, and full retina (P < 0.01) but not with the area of the foveal avascular zone.
CONCLUSION
The decrease in visual acuity in patients with BCR is associated with retinal vascular impairment. Vessel density of the retinal capillary plexuses may be a promising imaging biomarker for BCR disease severity.
Topics: Birdshot Chorioretinopathy; Capillaries; Chorioretinitis; Cross-Sectional Studies; Female; Fluorescein Angiography; Follow-Up Studies; Fovea Centralis; Fundus Oculi; Humans; Male; Middle Aged; Prospective Studies; Retinal Vessels; Severity of Illness Index; Tomography, Optical Coherence; Visual Acuity
PubMed: 28196058
DOI: 10.1097/IAE.0000000000001543 -
The Biochemical Journal Oct 2018The vitamin A derivative 11-retinaldehyde plays a pivotal role in vertebrate vision by serving as the chromophore of rod and cone visual pigments. In the initial step of... (Review)
Review
The vitamin A derivative 11-retinaldehyde plays a pivotal role in vertebrate vision by serving as the chromophore of rod and cone visual pigments. In the initial step of vision, a photon is absorbed by this chromophore resulting in its isomerization to an all- state and consequent activation of the visual pigment and phototransduction cascade. Spent chromophore is released from the pigments through hydrolysis. Subsequent photon detection requires the delivery of regenerated 11-retinaldehyde to the visual pigment. This conversion is achieved through a process known as the visual cycle. In this review, we will discuss the enzymes, binding proteins and transporters that enable the visual pigment renewal process with a focus on advances made during the past decade in our understanding of their structural biology.
Topics: Amino Acid Sequence; Animals; Crystallography, X-Ray; Humans; Protein Structure, Secondary; Retinal Pigment Epithelium; Retinal Pigments; Retinaldehyde; Vision, Ocular
PubMed: 30352831
DOI: 10.1042/BCJ20180193 -
BioEssays : News and Reviews in... Sep 2023The photocycle of visual opsins is essential to maintain the light sensitivity of the retina. The early physical observations of the rhodopsin photocycle by Böll and... (Review)
Review
The photocycle of visual opsins is essential to maintain the light sensitivity of the retina. The early physical observations of the rhodopsin photocycle by Böll and Kühne in the 1870s inspired over a century's worth of investigations on rhodopsin biochemistry. A single photon isomerizes the Schiff-base linked 11-cis-retinylidene chromophore of rhodopsin, converting it to the all-trans agonist to elicit phototransduction through photoactivated rhodopsin (Rho*). Schiff base hydrolysis of the agonist is a key step in the photocycle, not only diminishing ongoing phototransduction but also allowing for entry and binding of fresh 11-cis chromophore to regenerate the rhodopsin pigment and maintain light sensitivity. Many challenges have been encountered in measuring the rate of this hydrolysis, but recent advancements have facilitated studies of the hydrolysis within the native membrane environment of rhodopsin. These techniques can now be applied to study hydrolysis of agonist in other opsin proteins that mediate phototransduction or chromophore turnover. In this review, we discuss the progress that has been made in characterizing the rhodopsin photocycle and the journey to characterize the hydrolysis of its all-trans-retinylidene agonist.
Topics: Humans; Rhodopsin; Photophobia; Retinaldehyde; Retina
PubMed: 37454357
DOI: 10.1002/bies.202300068 -
Journal of Lipid Research 2021Driven by the energy of a photon, the visual pigments in rod and cone photoreceptor cells isomerize 11-cis-retinal to the all-trans configuration. This photochemical... (Review)
Review
Driven by the energy of a photon, the visual pigments in rod and cone photoreceptor cells isomerize 11-cis-retinal to the all-trans configuration. This photochemical reaction initiates the signal transduction pathway that eventually leads to the transmission of a visual signal to the brain and leaves the opsins insensitive to further light stimulation. For the eye to restore light sensitivity, opsins require recharging with 11-cis-retinal. This trans-cis back conversion is achieved through a series of enzymatic reactions composing the retinoid (visual) cycle. Although it is evident that the classical retinoid cycle is critical for vision, the existence of an adjunct pathway for 11-cis-retinal regeneration has been debated for many years. Retinal pigment epithelium (RPE)-retinal G protein-coupled receptor (RGR) has been identified previously as a mammalian retinaldehyde photoisomerase homologous to retinochrome found in invertebrates. Using pharmacological, genetic, and biochemical approaches, researchers have now established the physiological relevance of the RGR in 11-cis-retinal regeneration. The photoisomerase activity of RGR in the RPE and Müller glia explains how the eye can remain responsive in daylight. In this review, we will focus on retinoid metabolism in the eye and visual chromophore regeneration mediated by RGR.
Topics: Retinaldehyde
PubMed: 32493732
DOI: 10.1194/jlr.TR120000850 -
Redox Biology Aug 2022To facilitate the movement of retinoids through the visual cycle and to limit nonspecific chemical reaction, multiple mechanisms are utilized to handle these molecules...
To facilitate the movement of retinoids through the visual cycle and to limit nonspecific chemical reaction, multiple mechanisms are utilized to handle these molecules when not contained within the binding pocket of opsin. Vitamin A aldehyde is sequestered by reversible Schiff base formation with phosphatidylethanolamine (PE) and subsequently undergoes NADPH-dependent reduction. Otherwise inefficient handling of retinaldehyde can lead to the formation of fluorescent di-retinal compounds within the outer segments of photoreceptor cells. These bisretinoid fluorophores initiate photooxidative processes having adverse consequences for retina. Various carrier proteins confer water solubility and maintain the 11-cis-retinoid configuration. Mechanisms for sequestration of retinoid include the formation of a reversible Schiff base between retinaldehyde and taurine (A1-taurine, A1T), the most abundant amino acid in photoreceptor cells. Here we have undertaken to examine the effects of taurine depletion using the transport inhibitors guanidinoethyl sulfonate (GES) and β-alanine. Oral treatment of BALB/cJ mice with β-alanine reduced ocular A1T and the mice exhibited significantly lower scotopic and photopic a-wave amplitudes. As a secondary effect of retinal degeneration, A1T was not detected and taurine was significantly reduced in mice carrying a P23H opsin mutation. The thinning of ONL that is indicative of reduced photoreceptor cell viability in albino Abca4 mice was more pronounced in β-alanine treated mice. Treatment of agouti and albino Abca4 mice with β-alanine and GES was associated with reduced bisretinoid measured chromatographically. Consistent with a reduction in carbonyl scavenging activity by taurine, methylglyoxal-adducts were also increased in the presence of β-alanine. Taken together these findings support the postulate that A1T serves as a reservoir of vitamin A aldehyde, with diminished A1T explaining reduced photoreceptor light-sensitivity, accentuated ONL thinning in Abca4 mice and attenuated bisretinoid formation.
Topics: ATP-Binding Cassette Transporters; Animals; Mice; Opsins; Photoreceptor Cells; Retina; Retinaldehyde; Retinoids; Schiff Bases; Taurine; beta-Alanine
PubMed: 35809434
DOI: 10.1016/j.redox.2022.102386 -
Asia-Pacific Journal of Ophthalmology... Feb 2021The aim of this study was to assess possible correlation between the visual field and electroretinogram (ERG) parameters in birdshot chorioretinopathy (BCR).
PURPOSE
The aim of this study was to assess possible correlation between the visual field and electroretinogram (ERG) parameters in birdshot chorioretinopathy (BCR).
DESIGN
Retrospective cross-sectional study.
METHODS
This single-center study included 21 eyes of 11 patients with BCR with prior ERG and Goldmann kinetic perimetry. Generalized estimating equation was used for statistical analysis, and isopters V4e and I4e were modeled as separate outcomes with each parameter of ERG as the main independent variable. The main outcome measure was presence or absence of correlation between the Goldmann isopters and ERG parameters including the amplitudes and implicit times of dark adapted (DA) and light adapted (LA) a-waves and b-waves (DA 0.01, DA 3.0, DA 10.0, and LA 3.0) and LA 30 Hz.
RESULTS
There was a strong positive correlation between the size of isopter V4e and all the scotopic and photopic standard ERG amplitudes [P < 0.0001 for all, except LA 3.0 a-wave (P = 0.0019) and LA 30 Hz (P = 0.0026)]. For the implicit times, only DA 3.0 a-wave (P = 0.007) and LA 30 Hz (P < 0.0001) showed significant negative correlations. There were no correlations between the size of isopter I4e and any ERG amplitudes; however, 3 implicit times showed some negative correlation: DA 3.0 a-wave (P < 0.0001), DA 10.0 b-wave (P = 0.0251), and LA 3.0 b-wave (P < 0.0001).
CONCLUSIONS
In this study, the largest isopter of Glodmann visual field showed a strong positive correlation with all standard ERG amplitudes in BCR. This novel finding underscores the role of ERG as an objective visual function test in monitoring the disease activity.
Topics: Birdshot Chorioretinopathy; Cross-Sectional Studies; Electroretinography; Humans; Retina; Retrospective Studies; Visual Fields
PubMed: 33793442
DOI: 10.1097/APO.0000000000000374 -
Ceska a Slovenska Oftalmologie :... 2022The aim of this paper is to present an outline of forms of ocular manifestations of visceral larva migrans in children, as illustrated by the extensive photographic... (Review)
Review
The aim of this paper is to present an outline of forms of ocular manifestations of visceral larva migrans in children, as illustrated by the extensive photographic documentation. Ocular larval toxocariasis (OLT) has various clinical manifestations even in childhood age, in which age representation has an influence. The most common is presence of peripheral granuloma of the eye, frequently with a tractional vitreal streak leading from the retinal periphery to the optic nerve papilla. This is followed by granuloma of the posterior pole of the eye, usually reaching from the macular landscape to the central retinal periphery, always with vitritis. In children OLT may be manifested also in affliction of the optic nerve (cystic granuloma of the head of the optic nerve or neuropathy with vitreal reaction), fulminant endophthalmitis and in rare cases also diffuse chorioretinitis. The diagnosis rests upon a clinical ophthalmological finding, as well as laboratory examination of the levels of antibodies with potential eosinophilia. Histological examination may demonstrate spherical polypoid ossification in the choroid at the posterior pole of the eye as a consequence of fibrotisation and calcification, proceeding from the surrounding area of the absorbed larva. General combined treatment with antihelminthics and corticosteroids is arduous and does not always produce the desired effect in the sense of a satisfactory improvement of visual acuity. In differential diagnostics, manifestations of OLT in small children are still associated with retinoblastoma and a clinical picture of other intraocular diseases.
Topics: Animals; Child; Humans; Chorioretinitis; Endophthalmitis; Larva; Optic Nerve; Retina; Toxocariasis
PubMed: 36443030
DOI: 10.31348/2022/28 -
Journal of Lipid Research 2021Vitamin A aldehyde covalently bound to opsin protein is embedded in a phospholipid-rich membrane that supports photon absorption and phototransduction in photoreceptor... (Review)
Review
Vitamin A aldehyde covalently bound to opsin protein is embedded in a phospholipid-rich membrane that supports photon absorption and phototransduction in photoreceptor cell outer segments. Following absorption of a photon, the 11-cis-retinal chromophore of visual pigment in photoreceptor cells isomerizes to all-trans-retinal. To maintain photosensitivity 11-cis-retinal must be replaced. At the same time, however, all-trans-retinal has to be handled so as to prevent nonspecific aldehyde activity. Some molecules of retinaldehyde upon release from opsin are efficiently reduced to retinol. Other molecules are released into the lipid phase of the disc membrane where they form a conjugate [N-retinylidene-PE (NRPE)] through a Schiff base linkage with PE. The reversible formation of NRPE serves as a transient sink for retinaldehyde that is intended to return retinaldehyde to the visual cycle. However, if instead of hydrolyzing to PE and retinaldehyde, NRPE reacts with a second molecule of retinaldehyde, a synthetic pathway is initiated that leads to the formation of multiple species of unwanted bisretinoid fluorophores. We report on recently identified members of the bisretinoid family, some of which differ with respect to the acyl chains associated with the glycerol backbone. We discuss processing of the lipid moieties of these fluorophores in lysosomes of retinal pigment epithelial cells, their fluorescence characters, and new findings related to light- and iron-associated oxidation of bisretinoids.
Topics: Retinaldehyde
PubMed: 32371567
DOI: 10.1194/jlr.TR120000742 -
Advances in Experimental Medicine and... 2016Mutations in rhodopsin are one of the most common causes of retinitis pigmentosa (RP). Misfolding of rhodopsin can result in disruptions in cellular protein homeostasis,... (Review)
Review
Mutations in rhodopsin are one of the most common causes of retinitis pigmentosa (RP). Misfolding of rhodopsin can result in disruptions in cellular protein homeostasis, or proteostasis. There is currently no available treatment for RP. In this review, we discuss the different approaches currently being investigated for treatment of rhodopsin RP, focusing on the potential of manipulation of the proteostasis network as a therapeutic approach to combat retinal degeneration.
Topics: Animals; Disease Models, Animal; Genetic Predisposition to Disease; Humans; Molecular Targeted Therapy; Mutation; Proteostasis Deficiencies; Retinaldehyde; Retinitis Pigmentosa; Rhodopsin
PubMed: 26427449
DOI: 10.1007/978-3-319-17121-0_64 -
Turkish Journal of Ophthalmology Aug 2023To present the clinical and demographic characteristics, imaging findings, diagnosis and treatment approach in cases of cat scratch disease (CSD) with ocular involvement.
OBJECTIVES
To present the clinical and demographic characteristics, imaging findings, diagnosis and treatment approach in cases of cat scratch disease (CSD) with ocular involvement.
MATERIALS AND METHODS
The records of 19 patients followed-up and treated between 2010 and 2020, including detailed ophthalmological examinations, imaging findings, and treatment approach, were evaluated retrospectively.
RESULTS
Twenty-three eyes of 19 patients, 7 female (37%) and 12 male (63%), were included in the study. The mean age was 34.1±13.3 (range: 11-56) years, and the mean follow-up duration was 12.6±18.0 (range: 1-81) months. Unilateral involvement was observed in 15 cases (79%). Cat contact was reported in 14 cases (74%). In 6 cases (32%), flu-like symptoms were present before the ocular complaints. The mean visual acuity (VA) at presentation was 0.42±0.36 (range: 0.001-1.0). Anterior uveitis was observed in 3 eyes (13%). Posterior segment findings included neuroretinitis in 14 (61%), superficial retinal infiltrate(s) in 8 (35%), papillitis in 3 (13%), branch retinal artery occlusion in 2 (8%), and cilioretinal artery occlusion in 1 (4%) of the eyes. All cases were positive for immunglobulin (Ig)M and/or IgG. Systemic antibiotic therapy was administered to all patients. Intravenous pulse or oral corticosteroids were given, especially in cases with optic disc involvement. The mean final VA was 0.80±0.25 (range: 0.01-1.0).
CONCLUSION
CSD may present with different ocular involvement patterns. Apart from the classical neuroretinitis and macular star appearance, patients may present with isolated optic disc edema, branch retinal artery occlusion, and retinal infiltrations. In such patients, cat contact history and serology should be evaluated to differentiate CSD.
Topics: Female; Male; Humans; Cat-Scratch Disease; Retrospective Studies; Retina; Retinitis; Chorioretinitis; Retinal Artery Occlusion
PubMed: 37602640
DOI: 10.4274/tjo.galenos.2022.44692