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American Journal of Ophthalmology Aug 2021To determine classification criteria for acute retinal necrosis (ARN).
PURPOSE
To determine classification criteria for acute retinal necrosis (ARN).
DESIGN
Machine learning of cases with ARN and 4 other infectious posterior uveitides / panuveitides.
METHODS
Cases of infectious posterior uveitides / panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior uveitides / panuveitides. The resulting criteria were evaluated on the validation set.
RESULTS
Eight hundred three cases of infectious posterior uveitides / panuveitides, including 186 cases of ARN, were evaluated by machine learning. Key criteria for ARN included (1) peripheral necrotizing retinitis and either (2) polymerase chain reaction assay of an intraocular fluid specimen positive for either herpes simplex virus or varicella zoster virus or (3) a characteristic clinical appearance with circumferential or confluent retinitis, retinal vascular sheathing and/or occlusion, and more than minimal vitritis. Overall accuracy for infectious posterior uveitides / panuveitides was 92.1% in the training set and 93.3% (95% confidence interval 88.2, 96.3) in the validation set. The misclassification rates for ARN were 15% in the training set and 11.5% in the validation set.
CONCLUSIONS
The criteria for ARN had a reasonably low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research.
Topics: Adult; Female; Fluorescein Angiography; Fundus Oculi; Humans; Machine Learning; Male; Middle Aged; Retina; Retinal Necrosis Syndrome, Acute; Tomography, Optical Coherence
PubMed: 33845012
DOI: 10.1016/j.ajo.2021.03.057 -
Journal of Neuroinflammation Dec 2021Glaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells...
BACKGROUND
Glaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells (RGCs). Although the mechanisms underlying RGC apoptosis in glaucoma are extremely complicated, an abnormal cross-talk between retinal glial cells and RGCs is generally thought to be involved. However, how interaction of Müller cells and microglia, two types of glial cells, contributes to RGC injury is largely unknown.
METHODS
A mouse chronic ocular hypertension (COH) experimental glaucoma model was produced. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), transwell co-culture of glial cells, flow cytometry assay, ELISA, Ca image, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the interaction of Müller cells and microglia, and its underlying mechanisms in COH retina.
RESULTS
We first showed that Müller cell activation in mice with COH induced microglia activation through the ATP/P2X7 receptor pathway. The activation of microglia resulted in a significant increase in mRNA and protein levels of pro-inflammatory factors, such as tumor necrosis factor-α and interleukin-6. These inflammatory factors in turn caused the up-regulation of mRNA expression of pro-inflammatory factors in Müller cells through a positive feedback manner.
CONCLUSIONS
These findings provide robust evidence, for the first time, that retinal inflammatory response may be aggravated by an interplay between activated two types of glial cells. These results also suggest that to reduce the interplay between Müller cells and microglia could be a potential effective strategy for preventing the loss of RGCs in glaucoma.
Topics: Adenosine Triphosphate; Animals; Coculture Techniques; Cytokines; Ependymoglial Cells; Glaucoma; Macrophage Activation; Mice; Mice, Inbred C57BL; Microglia; Ocular Hypertension; Receptors, Purinergic P2X7; Retinal Ganglion Cells; Retinitis; Signal Transduction
PubMed: 34952606
DOI: 10.1186/s12974-021-02366-x -
Indian Journal of Ophthalmology Jul 2023To study the clinical presentation and treatment outcome of epidemic retinitis (ER) during pregnancy. (Observational Study)
Observational Study
PURPOSE
To study the clinical presentation and treatment outcome of epidemic retinitis (ER) during pregnancy.
METHODS
This is a retrospective, observational chart review of pregnant patients diagnosed with ER from January 2014 to February 2023. Demographic details, month of pregnancy at the onset of ocular symptoms, history of present illness, clinical manifestations, and treatment outcomes were studied.
RESULTS
In 9 years, ER was seen in 86 females, of whom 12 (13.9%) were pregnant. Twenty-one eyes of those 12 patients were studied. Most of the patients presented in the sixth month of pregnancy (range: 5-9 months, mean: 6.3 months). Physicians diagnosed viral exanthematous fever in six, typhoid in three, and suspected rickettsia in one patient. Medical termination of pregnancy (MTP) was performed in two patients before presentation. Weil-Felix test was positive in five, Brucella in one, WIDAL in three, and coronavirus disease 2019 (COVID-19) IgG and dengue IgG in one patient each. Oral antibiotics were given in five patients (two post-medical termination of pregnancy [MTP]) for the retinitis. All except four received oral steroids. Mean presenting corrected distant visual acuity (n = 21) was 20/125 (range: 20/20-20/20,000), which improved to (n = 18) 20/30 (range: 20/20-20/240). Macular edema (n = 11) resolved in 33.18 days (range: 20-50 days), and retinitis (n = 13) resolved in 58 days (range: 30-110 days). Ocular and systemic examination of newborn was possible in two and the babies were normal.
CONCLUSION
ER is seen commonly at the beginning of the third trimester. Lack of antibiotics may delay the resolution of retinitis. Ocular health needs to be assessed in larger series to conclude absence of retinal involvement in newborns.
Topics: Infant, Newborn; Female; Humans; Pregnancy; COVID-19; Retinitis; Retina; Anti-Bacterial Agents; Immunoglobulin G; Retrospective Studies
PubMed: 37417121
DOI: 10.4103/IJO.IJO_3169_22 -
Neurosciences (Riyadh, Saudi Arabia) Oct 2014Vision is perhaps the most important of all our senses, and gives us an immense amount of information regarding the outside world. The initial format in which this... (Review)
Review
Vision is perhaps the most important of all our senses, and gives us an immense amount of information regarding the outside world. The initial format in which this information reaches the retina are photons; particles of energy radiation of a given wavelength emitted or reflected from our surroundings. The brain itself however, perceives information in electrical signals via action potentials and changes in electrochemical gradients. The processes involved in the transduction of photons into electrical potentials will be the focus of this article. This review article summarizes the recent advances in understanding these complex pathways and provides an overview of the main molecules involved in the neurobiology of vision.
Topics: Action Potentials; Animals; Calcium Signaling; Cyclic GMP; G-Protein-Coupled Receptor Kinase 1; Humans; Opsins; Photons; Protein Conformation; Recoverin; Retina; Retinal Pigments; Retinal Rod Photoreceptor Cells; Retinaldehyde; Second Messenger Systems; Vision, Ocular
PubMed: 25274585
DOI: No ID Found -
The Journal of General Physiology May 1955The iodopsin system found in the cones of the chicken retina is identical with the rhodopsin system in its carotenoids. It differs only in the protein-the opsin -with...
The iodopsin system found in the cones of the chicken retina is identical with the rhodopsin system in its carotenoids. It differs only in the protein-the opsin -with which carotenoid combines. The cone protein may be called photopsin to distinguish it from the scotopsins of the rods. Iodopsin bleaches in the light to a mixture of photopsin and all-trans retinene. The latter is reduced by alcohol dehydrogenase and cozymase to all-trans vitamin A(1). Iodopsin is resynthesized from photopsin and a cis isomer of vitamin A, neovitamin Ab or the corresponding neoretinene b, the same isomer that forms rhodopsin. The synthesis of iodopsin from photopsin and neoretinene b is a spontaneous reaction. A second cis retinene, isoretinene a, forms iso-iodopsin (lambda(max) 510 mmicro). The bleaching of iodopsin in moderate light is a first-order reaction (Bliss). The synthesis of iodopsin from neoretinene b and opsin is second-order, like that of rhodopsin, but is very much more rapid. At 10 degrees C. the velocity constant for iodopsin synthesis is 527 times that for rhodopsin synthesis. Whereas rhodopsin is reasonably stable in solution from pH 4-9, iodopsin is stable only at pH 5-7, and decays rapidly at more acid or alkaline reactions. The sulfhydryl poison, p-chloromercuribenzoate, blocks the synthesis of iodopsin, as of rhodopsin. It also bleaches iodopsin in concentrations which do not attack rhodopsin. Hydroxylamine also bleaches iodopsin, yet does not poison its synthesis. Hydroxylamine acts by competing with the opsins for retinene. It competes successfully with chicken, cattle, or frog scotopsin, and hence blocks rhodopsin synthesis; but it is less efficient than photopsin in trapping retinene, and hence does not block iodopsin synthesis. Though iodopsin has not yet been prepared in pure form, its absorption spectrum has been computed by two independent procedures. This exhibits an alpha-band with lambda(max) 562 mmicro, a minimum at about 435 mmicro, and a small beta-band in the near ultraviolet at about 370 mmicro. The low concentration of iodopsin in the cones explains to a first approximation their high threshold, and hence their status as organs of daylight vision. The relatively rapid synthesis of iodopsin compared with rhodopsin parallels the relatively rapid dark adaptation of cones compared with rods. A theoretical relation is derived which links the logarithm of the visual sensitivity with the concentration of visual pigment in the rods and cones. Plotted in these terms, the course of rod and cone dark adaptation resembles closely the synthesis of rhodopsin and iodopsin in solution. The spectral sensitivities of rod and cone vision, and hence the Purkinje phenomenon, have their source in the absorption spectra of rhodopsin and iodopsin. In the chicken, for which only rough spectral sensitivity measurements are available, this relation can be demonstrated only approximately. In the pigeon the scotopic sensitivity matches the spectrum of rhodopsin; but the photopic sensitivity is displaced toward the red, largely or wholly through the filtering action of the colored oil globules in the pigeon cones. In cats, guinea pigs, snakes, and frogs, in which no such colored ocular structures intervene, the scotopic and photopic sensitivities match quantitatively the absorption spectra of rhodopsin and iodopsin. In man the scotopic sensitivity matches the absorption spectrum of rhodopsin; but the photopic sensitivity, when not distorted by the yellow pigmentations of the lens and macula lutea, lies at shorter wave lengths than iodopsin. This discrepancy is expected, for the human photopic sensitivity represents a composite of at least three classes of cone concerned with color vision.
Topics: Animals; Cats; Cattle; Chickens; Eye Proteins; Guinea Pigs; Retina; Retinal Cone Photoreceptor Cells; Retinal Pigments; Retinaldehyde; Rhodopsin; Rod Opsins
PubMed: 14367777
DOI: 10.1085/jgp.38.5.623 -
Canadian Medical Association Journal Jul 1963Retinal burns can be produced by direct gazing at the sun. This lesion is caused by the thermal effects of the visible and near infrared rays focused on the pigment...
Retinal burns can be produced by direct gazing at the sun. This lesion is caused by the thermal effects of the visible and near infrared rays focused on the pigment structure behind the retina. It is rarely seen, as the normal eye will tolerate only fleeting glances at the sun, but is fairly common during a solar eclipse. A case of solar retinitis is presented in which treatment with corticosteroids lessened the retinal edema but the patient suffered a bilateral central scotoma and vision reduced to the 20/40 level. In viewing a solar eclipse a No. 4 density filter is recommended; as a rough test this filter will abolish the readability of print on a 60-watt incandescent frosted electric light bulb.
Topics: Cicatrix; Eye Injuries; Humans; Infrared Rays; Light; Male; Retina; Retinal Diseases; Retinitis; Scotoma; Sunlight
PubMed: 13977409
DOI: No ID Found -
The Journal of Biological Chemistry May 2023Dry age-related macular degeneration (AMD) and recessive Stargardt's disease (STGD1) lead to irreversible blindness in humans. The accumulation of all-trans-retinal...
Dry age-related macular degeneration (AMD) and recessive Stargardt's disease (STGD1) lead to irreversible blindness in humans. The accumulation of all-trans-retinal (atRAL) induced by chaos in visual cycle is closely associated with retinal atrophy in dry AMD and STGD1 but its critical downstream signaling molecules remain ambiguous. Here, we reported that activation of eukaryotic translation initiation factor 2α (eIF2α) by atRAL promoted retinal degeneration and photoreceptor loss through activating c-Jun N-terminal kinase (JNK) signaling-dependent apoptosis and gasdermin E (GSDME)-mediated pyroptosis. We determined that eIF2α activation by atRAL in photoreceptor cells resulted from endoplasmic reticulum homeostasis disruption caused at least in part by reactive oxygen species production, and it activated JNK signaling independent of and dependent on activating transcription factor 4 and the activating transcription factor 4/transcription factor C/EBP homologous protein (CHOP) axis. CHOP overexpression induced apoptosis of atRAL-loaded photoreceptor cells through activating JNK signaling rather than inhibiting the expression of antiapoptotic gene Bcl2. JNK activation by eIF2α facilitated photoreceptor cell apoptosis caused by atRAL via caspase-3 activation and DNA damage. Additionally, we demonstrated that eIF2α was activated in neural retina of light-exposed Abca4Rdh8 mice, a model that shows severe defects in atRAL clearance and displays primary features of human dry AMD and STGD1. Of note, inhibition of eIF2α activation by salubrinal effectively ameliorated retinal degeneration and photoreceptor apoptosis in Abca4Rdh8 mice upon light exposure. The results of this study suggest that eIF2α is an important target to develop drug therapies for the treatment of dry AMD and STGD1.
Topics: Animals; Humans; Mice; Activating Transcription Factor 4; Apoptosis; ATP-Binding Cassette Transporters; Photoreceptor Cells, Vertebrate; Retina; Retinal Degeneration; Retinal Pigment Epithelium; Retinaldehyde; Stargardt Disease; Eukaryotic Initiation Factor-2
PubMed: 37031820
DOI: 10.1016/j.jbc.2023.104686 -
Indian Journal of Ophthalmology Mar 2022To identify factors other than macular edema and retinitis location responsible for poor visual outcomes in epidemic retinitis (ER). (Observational Study)
Observational Study
PURPOSE
To identify factors other than macular edema and retinitis location responsible for poor visual outcomes in epidemic retinitis (ER).
METHODS
A.
UNLABELLED
retrospective, observational, comparative study. Eyes with corrected distant visual acuity (CDVA) 20/200 or worse at resolution formed Group A. Eyes with central macular thickness (CMT) 600 μm or worse and retinitis within 1500 μm to foveal center at the presentation, but improved to CDVA 20/200 or better at the resolution formed Group B. The patient's history, clinical presentation, imaging, and treatment outcomes were studied and the factors responsible for the final visual outcomes were compared in both groups.
RESULTS
Groups A and B included 25 eyes each. The mean CDVA at the presentation was 20/400 (range: 20/125-20000) and 20/320 (range: 20/80-20000), and mean CMT at the presentation was 948.5 μm (range: 520-1553) and 912.2 μm (range: 615-1250) in Groups A and B, respectively. All eyes except 1 (Group A) had retinitis lesions within 1500 μm of foveal center. The mean CDVA at the resolution was 20/400 (range: 20/200-20/20000) and 20/40 (range: 20/20-20/80) in Groups A and B, respectively. Older age, male gender, diabetic status, delayed presentation, poor presenting CDVA, bilaterality, presence of keratic precipitates, disk pallor, retinal thinning, and subfoveal deposits had a statistically significant association, whereas the absence of skin rash, ellipsoid zone loss, negative WIDAL, Weil-Felix test, and delayed doxycycline therapy or use of steroids without doxycycline had a statistically insignificant association with poor visual outcomes.
CONCLUSION
Apart from presenting CMT and location of retinitis, multiple demographic, clinical, and imaging factors can be implicated for poor visual outcomes.
Topics: Fovea Centralis; Humans; Macular Edema; Male; Retinitis; Retrospective Studies; Tomography, Optical Coherence; Visual Acuity
PubMed: 35225539
DOI: 10.4103/ijo.IJO_1153_21 -
Indian Journal of Ophthalmology May 2024To study the choroidal thickness (CT) and central macular thickness (CMT) in post-fever retinitis (PFR) and their correlation with visual acuity and treatment. (Observational Study)
Observational Study
PURPOSE
To study the choroidal thickness (CT) and central macular thickness (CMT) in post-fever retinitis (PFR) and their correlation with visual acuity and treatment.
METHODS
A retrospective, observational study of patients presenting with PFR from 2013 to 2021 and with spectral domain optical coherence tomography (SD-OCT) (Heidelberg®, SpectralisTM, Heidelberg, Germany) images were included. The CT and CMT were measured at presentation and at the final visit. The CT was measured subfoveally and at points 2000 µm superior, inferior, medial, and lateral from the fovea using the caliper tool.
RESULTS
Seventy-nine eyes of 65 patients were included for this study. The mean age was 39.03 (±16.00) years with female preponderance of 53.84% (n = 35). Mean follow-up duration was 30 days. Mean CT at presentation and at follow-up was 254.12 µm and 241.51 µm, respectively. CT was decreased in majority of the eyes 67.1% (n = 53) from their baseline value. Mean CMTs at presentation and final visit were 454.8 µm and 223.7 µm, respectively. Best corrected visual acuity had a positive correlation with CMT (r = 0.340; P = 0.002) and negligible correlation with CT. A significant decrease in the mean CT was noted in patients who received doxycycline either alone or in combination with a steroid as compared to those who did not receive any treatment (P < 0.001). The significance of which is unknown presently.
CONCLUSION
CMT has a greater role in determining the final visual outcome than CT. CT can be reduced post-treatment with no effect on vision.
Topics: Humans; Female; Retrospective Studies; Male; Tomography, Optical Coherence; Adult; Choroid; Visual Acuity; Macula Lutea; Retinitis; Follow-Up Studies; Middle Aged; Eye Infections, Bacterial; Young Adult; Anti-Bacterial Agents; Adolescent
PubMed: 38648435
DOI: 10.4103/IJO.IJO_1557_23 -
Biochimica Et Biophysica Acta May 2014Cone visual pigments are visual opsins that are present in vertebrate cone photoreceptor cells and act as photoreceptor molecules responsible for photopic vision. Like... (Review)
Review
Cone visual pigments are visual opsins that are present in vertebrate cone photoreceptor cells and act as photoreceptor molecules responsible for photopic vision. Like the rod visual pigment rhodopsin, which is responsible for scotopic vision, cone visual pigments contain the chromophore 11-cis-retinal, which undergoes cis-trans isomerization resulting in the induction of conformational changes of the protein moiety to form a G protein-activating state. There are multiple types of cone visual pigments with different absorption maxima, which are the molecular basis of color discrimination in animals. Cone visual pigments form a phylogenetic sister group with non-visual opsin groups such as pinopsin, VA opsin, parapinopsin and parietopsin groups. Cone visual pigments diverged into four groups with different absorption maxima, and the rhodopsin group diverged from one of the four groups of cone visual pigments. The photochemical behavior of cone visual pigments is similar to that of pinopsin but considerably different from those of other non-visual opsins. G protein activation efficiency of cone visual pigments is also comparable to that of pinopsin but higher than that of the other non-visual opsins. Recent measurements with sufficient time-resolution demonstrated that G protein activation efficiency of cone visual pigments is lower than that of rhodopsin, which is one of the molecular bases for the lower amplification of cones compared to rods. In this review, the uniqueness of cone visual pigments is shown by comparison of their molecular properties with those of non-visual opsins and rhodopsin. This article is part of a Special Issue entitled: Retinal Proteins - You can teach an old dog new tricks.
Topics: Animals; Color Vision; Evolution, Molecular; Humans; Models, Molecular; Molecular Conformation; Opsins; Phylogeny; Retinal Cone Photoreceptor Cells; Retinaldehyde; Rhodopsin
PubMed: 24021171
DOI: 10.1016/j.bbabio.2013.08.009