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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 -
Retina (Philadelphia, Pa.) Sep 2023To describe a case series of a special subtype of punctate inner choroidopathy with solitary lesions in the macular area and named solitary punctate chorioretinitis. (Observational Study)
Observational Study
PURPOSE
To describe a case series of a special subtype of punctate inner choroidopathy with solitary lesions in the macular area and named solitary punctate chorioretinitis.
METHODS
This retrospective observational study clinically evaluated 12 eyes from 12 patients diagnosed as punctate inner choroidopathy with solitary lesions. Demographic data and multimodal imaging features were analyzed for the included patients.
RESULTS
All the included patients were Chinese and of Han ethnicity. The median age of the included patients was 29.5 years (range: 25-40 years). Most patients (11/12, 91.67%) were myopic, with median refraction errors of -4.4 diopters (D) (range: -8.5 to 0 D). Solitary chorioretinitis lesions were yellow‒white and appeared hyperfluorescent during the entire phase of fundus fluorescein angiography without leakage (9/12, 75%) and hypofluorescent on indocyanine green angiography (11/11, 100%). On spectral domain optical coherence tomography, active inflammatory lesions appeared as isolated, heterogeneous, moderately reflective material at the outer retina (10/12, 83.33%) in the fovea or parafoveal region with disruption of the outer retinal layers. When the inflammatory lesions regressed, the moderately reflective materials in the outer retina were absorbed or regressed with outer retinal tissue loss. Additional sequelae of lesion regression included focal choroidal excavation and intraretinal cystoid space. Secondary choroidal neovascularization was noticed in 2 eyes (2/12, 16.67%).
CONCLUSION
Solitary punctate chorioretinitis is a rare and unique subtype of punctate inner choroidopathy. Solitary punctate chorioretinitis may also be an unrecognized etiology of some forms of focal choroidal excavation and idiopathic choroidal neovascularization.
Topics: Adult; Humans; Chorioretinitis; Choroidal Neovascularization; Fluorescein Angiography; Retina; White Dot Syndromes; East Asian People
PubMed: 37607393
DOI: 10.1097/IAE.0000000000003828 -
International Journal of Molecular... Feb 2019The retinal pigment epithelium (RPE) forms the outer blood⁻retina barrier and facilitates the transepithelial transport of glucose into the outer retina via GLUT1.... (Review)
Review
The retinal pigment epithelium (RPE) forms the outer blood⁻retina barrier and facilitates the transepithelial transport of glucose into the outer retina via GLUT1. Glucose is metabolized in photoreceptors via the tricarboxylic acid cycle (TCA) and oxidative phosphorylation (OXPHOS) but also by aerobic glycolysis to generate glycerol for the synthesis of phospholipids for the renewal of their outer segments. Aerobic glycolysis in the photoreceptors also leads to a high rate of production of lactate which is transported out of the subretinal space to the choroidal circulation by the RPE. Lactate taken up by the RPE is converted to pyruvate and metabolized via OXPHOS. Excess lactate in the RPE is transported across the basolateral membrane to the choroid. The uptake of glucose by cone photoreceptor cells is enhanced by rod-derived cone viability factor (RdCVF) secreted by rods and by insulin signaling. Together, the three cells act as symbiotes: the RPE supplies the glucose from the choroidal circulation to the photoreceptors, the rods help the cones, and both produce lactate to feed the RPE. In age-related macular degeneration this delicate ménage à trois is disturbed by the chronic infiltration of inflammatory macrophages. These immune cells also rely on aerobic glycolysis and compete for glucose and produce lactate. We here review the glucose metabolism in the homeostasis of the outer retina and in macrophages and hypothesize what happens when the metabolism of photoreceptors and the RPE is disturbed by chronic inflammation.
Topics: Animals; Cell Survival; Disease Susceptibility; Energy Metabolism; Genetic Predisposition to Disease; Humans; Macrophages; Macular Degeneration; Oxidation-Reduction; Retina; Retinal Cone Photoreceptor Cells; Retinal Pigment Epithelium; Retinal Rod Photoreceptor Cells; Retinitis
PubMed: 30754662
DOI: 10.3390/ijms20030762 -
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 -
Progress in Retinal and Eye Research Mar 2012The retina exhibits an inherent autofluorescence that is imaged ophthalmoscopically as fundus autofluorescence. In clinical settings, fundus autofluorescence examination... (Review)
Review
The retina exhibits an inherent autofluorescence that is imaged ophthalmoscopically as fundus autofluorescence. In clinical settings, fundus autofluorescence examination aids in the diagnosis and follow-up of many retinal disorders. Fundus autofluorescence originates from the complex mixture of bisretinoid fluorophores that are amassed by retinal pigment epithelial (RPE) cells as lipofuscin. Unlike the lipofuscin found in other cell-types, this material does not form as a result of oxidative stress. Rather, the formation is attributable to non-enzymatic reactions of vitamin A aldehyde in photoreceptor cells; transfer to RPE occurs upon phagocytosis of photoreceptor outer segments. These fluorescent pigments accumulate even in healthy photoreceptor cells and are generated as a consequence of the light capturing function of the cells. Nevertheless, the formation of this material is accelerated in some retinal disorders including recessive Stargardt disease and ELOVL4-related retinal degeneration. As such, these bisretinoid side-products are implicated in the disease processes that threaten vision. In this article, we review our current understanding of the composition of RPE lipofuscin, the structural characteristics of the various bisretinoids, their related spectroscopic features and the biosynthetic pathways by which they form. We will revisit factors known to influence the extent of the accumulation and therapeutic strategies being used to limit bisretinoid formation. Given their origin from vitamin A aldehyde, an isomer of the visual pigment chromophore, it is not surprising that the bisretinoids of retina are light sensitive molecules. Accordingly, we will discuss recent findings that implicate the photodegradation of bisretinoid in the etiology of age-related macular degeneration.
Topics: Animals; Cattle; Fluorescence; Humans; Lipofuscin; Macular Degeneration; Mice; Molecular Structure; Rats; Retinal Pigment Epithelium; Retinaldehyde; Retinoids; Spectrometry, Fluorescence
PubMed: 22209824
DOI: 10.1016/j.preteyeres.2011.12.001 -
Nutrients Nov 2016The visual system produces visual chromophore, 11--retinal from dietary vitamin A, all--retinol making this vitamin essential for retinal health and function. These... (Review)
Review
The visual system produces visual chromophore, 11--retinal from dietary vitamin A, all--retinol making this vitamin essential for retinal health and function. These metabolic events are mediated by a sequential biochemical process called the visual cycle. Retinol dehydrogenases (RDHs) are responsible for two reactions in the visual cycle performed in retinal pigmented epithelial (RPE) cells, photoreceptor cells and Müller cells in the retina. RDHs in the RPE function as 11--RDHs, which oxidize 11--retinol to 11--retinal in vivo. RDHs in rod photoreceptor cells in the retina work as all--RDHs, which reduce all--retinal to all--retinol. Dysfunction of RDHs can cause inherited retinal diseases in humans. To facilitate further understanding of human diseases, mouse models of RDHs-related diseases have been carefully examined and have revealed the physiological contribution of specific RDHs to visual cycle function and overall retinal health. Herein we describe the function of RDHs in the RPE and the retina, particularly in rod photoreceptor cells, their regulatory properties for retinoid homeostasis and future therapeutic strategy for treatment of retinal diseases.
Topics: Alcohol Oxidoreductases; Animals; Ependymoglial Cells; Genetic Predisposition to Disease; Humans; Mutation; Oxidation-Reduction; Phenotype; Retinal Diseases; Retinal Pigment Epithelium; Retinal Rod Photoreceptor Cells; Retinaldehyde; Vision, Ocular; Vitamin A
PubMed: 27879662
DOI: 10.3390/nu8110746 -
The Journal of Biological Chemistry Jan 2012Visual perception in humans occurs through absorption of electromagnetic radiation from 400 to 780 nm by photoreceptors in the retina. A photon of visible light carries... (Review)
Review
Visual perception in humans occurs through absorption of electromagnetic radiation from 400 to 780 nm by photoreceptors in the retina. A photon of visible light carries a sufficient amount of energy to cause, when absorbed, a cis,trans-geometric isomerization of the 11-cis-retinal chromophore, a vitamin A derivative bound to rhodopsin and cone opsins of retinal photoreceptors. The unique biochemistry of these complexes allows us to reliably and reproducibly collect continuous visual information about our environment. Moreover, other nonconventional retinal opsins such as the circadian rhythm regulator melanopsin also initiate light-activated signaling based on similar photochemistry.
Topics: Animals; Circadian Rhythm; Cone Opsins; Humans; Mice; Photons; Photoreceptor Cells, Vertebrate; Retinaldehyde; Rhodopsin; Rod Opsins; Vision, Ocular; Visual Perception
PubMed: 22074921
DOI: 10.1074/jbc.R111.301150 -
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 -
BioMed Research International 2014The application of perfluorocarbon liquids has been well acclaimed in vitreoretinal surgery. Its unique physical properties make it an ideal intraoperative tool to... (Review)
Review
The application of perfluorocarbon liquids has been well acclaimed in vitreoretinal surgery. Its unique physical properties make it an ideal intraoperative tool to improve the efficiency and safety of surgical procedures in complicated cases. The main functions of perfluorocarbon liquids in vitreoretinal surgery include relocating and fixing the detached retina, displacing the subretinal and subchoroidal to fluid anteriorly, revealing proliferative vitreous retinopathy (PVR) for further maneuvers, protecting the macula from exposure to chemicals with potential toxicity, and assisting the removal of foreign body. The related clinical applications include retinal detachment with severe proliferative vitreoretinopathy, giant tear, diabetic retinopathy (DR), retinopathy of prematurity (ROP), and posterior dislocated crystalline and intraocular lenses. The application of perfluorocarbon liquids has been expended over the past fewer years. Several PFCLs related ocular inflammations have been observed in in vitro studies, animal studies, and clinical follow-up. The complete removal of PFCLs is recommended at the end of the surgery in most cases.
Topics: Fluorocarbons; Humans; Ophthalmic Solutions; Premedication; Retinal Detachment; Retinitis; Solutions; Treatment Outcome; Vitreoretinal Surgery
PubMed: 24800216
DOI: 10.1155/2014/250323 -
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