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Ocular Immunology and Inflammation 2022To report the cytopathology of vitreous biopsy samples in patients with acute retinal necrosis (ARN) who underwent pars plana vitrectomy (PPV). We also describe two...
PURPOSE
To report the cytopathology of vitreous biopsy samples in patients with acute retinal necrosis (ARN) who underwent pars plana vitrectomy (PPV). We also describe two patients with unique clinical courses, cytopathologic findings, and immune response.
METHODS
A retrospective review of patients with ARN who developed retinal detachment (RD) and underwent PPV from 22011 to 2019 at the Emory Eye Center was performed to assess cytopathology findings of vitreous biopsy samples. Patient demographics and laboratory testing including aqueous humor PCR for viral pathogens were recorded. Additional clinical details abstracted included intravitreal injections, surgical procedures, and vitreous cytopathological reports including immunohistochemistry findings.
RESULTS
Fourteen eyes of 12 patients with RD were reviewed. Ten eyes showed HSV DNA (71%) and 4 demonstrated VZV DNA (29%). All eyes received intravitreal antivirals (i.e. ganciclovir or foscarnet) with a median of 8.5 intravitreal injections per eye. Diagnoses prompting PPV included tractional RD in 14 eyes (100%), rhegmatogenous RD in 8 eyes (57%), vitreous hemorrhage in 4 eyes (29%) and vitreous opacity in 4 (29%). Ophthalmic pathology reports showed lymphocyte populations in 10 eyes (71%) with a CD3 + T-cell predominance in two patients where immunohistochemistry of CD3+ and CD20+ for T- and B-cell populations was performed. Observed immune cell populations included macrophages or histiocytes (11 eyes, 79%) and polymorphonuclear cells in 4 eyes (29%). Initial median VA was 2.5 (IQR 2.0-3.0) and improved to 2.0 (IQR 1.48-3.00, = .48) at 6-months and 1.8 (IQR 1.2-3.0, = .45) at 12 months follow-up.
CONCLUSIONS
Our cohort of ARN patients undergoing PPV show a spectrum of immunologic findings with the majority demonstrating a lymphocytic response. Histiocytes, macrophages, and PMNs were also observed. Cytopathologic and immunologic studies suggest that both innate and adaptive immunity are responsible for the clinical disease findings observed in ARN. The variability of the response to treatment in patients with ARN may reflect patient-to-patient differences in their antigen-specific immune response. Understanding the immunologic response associated with ARN may provide valuable information regarding the dosing and timing of treatment.
Topics: Humans; Retinal Necrosis Syndrome, Acute; Cytology
PubMed: 34242097
DOI: 10.1080/09273948.2021.1922926 -
Cell Reports Aug 2023In daylight, demand for visual chromophore (11-cis-retinal) exceeds supply by the classical visual cycle. This shortfall is compensated, in part, by the retinal...
In daylight, demand for visual chromophore (11-cis-retinal) exceeds supply by the classical visual cycle. This shortfall is compensated, in part, by the retinal G-protein-coupled receptor (RGR) photoisomerase, which is expressed in both the retinal pigment epithelium (RPE) and in Müller cells. The relative contributions of these two cellular pools of RGR to the maintenance of photoreceptor light responses are not known. Here, we use a cell-specific gene reactivation approach to elucidate the kinetics of RGR-mediated recovery of photoreceptor responses following light exposure. Electroretinographic measurements in mice with RGR expression limited to either cell type reveal that the RPE and a specialized subset of Müller glia contribute both to scotopic and photopic function. We demonstrate that 11-cis-retinal formed through photoisomerization is rapidly hydrolyzed, consistent with its role in a rapid visual pigment regeneration process. Our study shows that RGR provides a pan-retinal sink for all-trans-retinal released under sustained light conditions and supports rapid chromophore regeneration through the photic visual cycle.
Topics: Animals; Mice; Retinal Pigment Epithelium; Retinaldehyde; Retinal Pigments; Receptors, G-Protein-Coupled; Neuroglia; Retinal Cone Photoreceptor Cells
PubMed: 37585292
DOI: 10.1016/j.celrep.2023.112982 -
Experimental Eye Research Oct 2019Angiotensin II and aldosterone are the main effectors of the renin-angiotensin aldosterone system (RAAS) and have a central role in hypertension as well as... (Review)
Review
Angiotensin II and aldosterone are the main effectors of the renin-angiotensin aldosterone system (RAAS) and have a central role in hypertension as well as cardiovascular and renal disease. The localization of RAAS components within the retina has led to studies investigating the roles of angiotensin II, aldosterone and the counter regulatory arm of the pathway in vision-threatening retinopathies. This review will provide a brief overview of RAAS components as well as the vascular pathology that develops in the retinal diseases, retinopathy of prematurity, diabetic retinopathy and neovascular age-related macular degeneration. The review will discuss pre-clinical and clinical evidence that modulation of the RAAS alters the development of vasculopathy and inflammation in the aforementioned retinopathies, as well as the emerging role of aldosterone and the mineralocorticoid receptor in central serous chorioretinopathy.
Topics: Aldosterone; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Diabetic Retinopathy; Humans; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Retinal Vessels; Retinitis; Retinopathy of Prematurity; Wet Macular Degeneration
PubMed: 31425690
DOI: 10.1016/j.exer.2019.107766 -
American Journal of Ophthalmology Aug 2021To determine classification criteria for birdshot chorioretinitis.
PURPOSE
To determine classification criteria for birdshot chorioretinitis.
DESIGN
Machine learning of cases with birdshot chorioretinitis and 8 other posterior uveitides.
METHODS
Cases of posterior uveitides 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
One thousand sixty-eight cases of posterior uveitides, including 207 cases of birdshot chorioretinitis, were evaluated by machine learning. Key criteria for birdshot chorioretinitis included a multifocal choroiditis with (1) the characteristic appearance of a bilateral multifocal choroiditis with cream-colored or yellow-orange, oval or round choroidal spots ("birdshot" spots); (2) absent to mild anterior chamber inflammation; and (3) absent to moderate vitreous inflammation; or multifocal choroiditis with positive HLA-A29 testing and either classic "birdshot spots" or characteristic imaging on indocyanine green angiography. Overall accuracy for posterior uveitides was 93.9% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for birdshot chorioretinitis were 10% in the training set and 0% in the validation set.
CONCLUSIONS
The criteria for birdshot chorioretinitis had a low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research.
Topics: Birdshot Chorioretinopathy; Choroid; Consensus; Female; Fluorescein Angiography; Fundus Oculi; Humans; Machine Learning; Male; Middle Aged; Retina
PubMed: 33845003
DOI: 10.1016/j.ajo.2021.03.059 -
International Ophthalmology Jan 2021To describe two distinct presentations of syphilitic fundus features in a series of patients with ocular syphilis.
PURPOSE
To describe two distinct presentations of syphilitic fundus features in a series of patients with ocular syphilis.
METHODS
This is a retrospective, interventional case series of 22 eyes from 16 serology confirmed cases. Clinical examination, fluorescein angiography, and optical coherence tomography were performed at presentation and following high-dose intravenous penicillin G.
RESULTS
In our cohort, the mean age was 47.6 years (range 24-59 years) and 14 patients were male (87.5%), 11 patients were positive for human immunodeficiency virus (68.8%), and 6 had bilateral involvement (37.5%). Mean best-corrected visual acuity improved from 0.99 ± 0.79 logarithm of the minimal angle of resolution (LogMAR) at the time of presentation to 0.29 ± 0.36 LogMAR on final visit (P < 0.01). Posterior segment examinations in eyes with retinitis showed two distinct types (1) discrete, placoid lesions in the macula consistent with acute syphilitic posterior placoid chorioretinitis or (2) punctate inner retinitis with corresponding fluorescein pooling in a segmental pattern. These findings rapidly resolved after antibiotic therapy.
CONCLUSION
In the era of resurgence, ocular syphilis may present with two phenotypes of discrete retinal lesions. Recognition of the characteristic ocular features may help make the diagnosis and monitor treatment response.
Topics: Adult; Chorioretinitis; Eye Infections, Bacterial; Female; Fluorescein Angiography; Humans; Male; Middle Aged; Retinitis; Retrospective Studies; Syphilis; Tomography, Optical Coherence; Young Adult
PubMed: 32875361
DOI: 10.1007/s10792-020-01569-0 -
Ocular Immunology and Inflammation Jul 2021: To study treatment outcomes with and without oral corticosteroids in epidemic retinitis (ER).: A retrospective, observational study of 35 eyes of 29 patients diagnosed... (Comparative Study)
Comparative Study
: To study treatment outcomes with and without oral corticosteroids in epidemic retinitis (ER).: A retrospective, observational study of 35 eyes of 29 patients diagnosed as ER. Days taken for resolution of macular edema and retinitis lesions were compared in patients treated with oral antibiotics (Group 1) and with corticosteroids-antibiotics combination (Group 2).: Eighteen eyes of 14 patients and 17 eyes of 15 patients formed Groups 1 and 2, respectively. At the presentation, mean best-corrected visual acuity (BCVA) was 40 and 44 letters and mean central macular thickness was 648 (±243) and 626 (±256) microns in Groups 1 and 2, respectively. Macular edema resolved in 30.83 and 31.94 days; retinitis lesions resolved in 36.71 and 41.41 days in Groups 1 and 2, respectively. BCVA improved to 74 and 77 letters in Groups 1 and 2, respectively.: ER with macular edema can be well managed without corticosteroids.
Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Bacterial Agents; Female; Glucocorticoids; Humans; Macular Edema; Male; Middle Aged; Retinitis; Retrospective Studies; Treatment Outcome; Visual Acuity; Young Adult
PubMed: 31961210
DOI: 10.1080/09273948.2019.1704792 -
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 -
Graefe's Archive For Clinical and... Oct 2022In many retinal pathological conditions, rod and cone degeneration differs. For example, the early-onset maculopathy Stargardts disease type 1 (STGD1) is typified by... (Review)
Review
PURPOSE
In many retinal pathological conditions, rod and cone degeneration differs. For example, the early-onset maculopathy Stargardts disease type 1 (STGD1) is typified by loss of cones while rods are often less affected. We wanted to examine whether there exist intrinsic membrane differences between rods and cones that might explain such features.
METHODS
Abca4 mRNA and protein levels were quantified in rod- and cone-enriched samples from wild-type and Nrl mice retinas; rod- and cone-enriched outer segments (ROS and COS respectively) were prepared from pig retinas, and total lipids were analyzed by flame ionization, chromatography, and tandem mass spectrometry. Immunohistochemical staining of cone-rich rodent Arvicanthis ansorgei retinas was conducted, and ultra-high performance liquid chromatography of lipid species in porcine ROS and COS was performed.
RESULTS
Abca4 mRNA and Abca4 protein content was significantly higher (50-300%) in cone compared to rod-enriched samples. ROS and COS displayed dramatic differences in several lipids, including very long chain poly-unsaturated fatty acids (VLC-PUFAs), especially docosahexaenoic acid (DHA, 22:6n-3): ROS 20.6% DHA, COS 3.3% (p < 0.001). VLC-PUFAs (> 50 total carbons) were virtually absent from COS. COS were impoverished (> 6× less) in phosphatidylethanolamine compared to ROS. ELOVL4 ("ELOngation of Very Long chain fatty acids 4") antibody labelled Arvicanthis cones only very weakly compared to rods. Finally, there were large amounts (905 a.u.) of the bisretinoid A2PE in ROS, whereas it was much lower (121 a.u., ~ 7.5-fold less) in COS fractions. In contrast, COS contained fivefold higher amounts of all-trans-retinal dimer (115 a.u. compared to 22 a.u. in rods).
CONCLUSIONS
Compared to rods, cones expressed higher levels of Abca4 mRNA and Abca4 protein, were highly impoverished in PUFA (especially DHA) and phosphatidylethanolamine, and contained significant amounts of all-trans-retinal dimer. Based on these and other data, we propose that in contrast to rods, cones are preferentially vulnerable to stress and may die through direct cellular toxicity in pathologies such as STGD1.
Topics: Animals; Docosahexaenoic Acids; Murinae; Phosphatidylethanolamines; RNA, Messenger; Reactive Oxygen Species; Retinal Cone Photoreceptor Cells; Retinal Degeneration; Retinaldehyde; Swine
PubMed: 35524799
DOI: 10.1007/s00417-022-05684-9 -
Molecular Nutrition & Food Research Aug 2019Zinc is an essential nutrient for human health. It plays key roles in maintaining protein structure and stability, serves as catalytic factor for many enzymes, and... (Review)
Review
Zinc is an essential nutrient for human health. It plays key roles in maintaining protein structure and stability, serves as catalytic factor for many enzymes, and regulates diverse fundamental cellular processes. Zinc is important in affecting signal transduction and, in particular, in the development and integrity of the immune system, where it affects both innate and adaptive immune responses. The eye, especially the retina-choroid complex, has an unusually high concentration of zinc compared to other tissues. The highest amount of zinc is concentrated in the retinal pigment epithelium (RPE) (RPE-choroid, 292 ± 98.5 µg g dry tissue), followed by the retina (123 62.2 µg g dry tissue). The interplay between zinc and inflammation has been explored in other parts of the body but, so far, has not been extensively researched in the eye. Several lines of evidence suggest that ocular zinc concentration decreases with age, especially in the context of age-related disease. Thus, a hypothesis that retinal function could be modulated by zinc nutrition is proposed, and subsequently trialled clinically. In this review, the distribution and the potential role of zinc in the retina-choroid complex is outlined, especially in relation to inflammation and immunity, and the clinical studies to date are summarized.
Topics: Aging; Dietary Supplements; Gastrointestinal Microbiome; Humans; Immunity, Humoral; Immunity, Innate; Macular Degeneration; Retina; Retinitis; Zinc
PubMed: 31148351
DOI: 10.1002/mnfr.201801049 -
Retinal Cases & Brief Reports Nov 2022To describe a patient with recurrent acute retinal necrosis (ARN), her treatment, and propose a possible pathophysiologic mechanism.
PURPOSE
To describe a patient with recurrent acute retinal necrosis (ARN), her treatment, and propose a possible pathophysiologic mechanism.
METHOD
Case report.
RESULTS
A 4-year-old girl presented elsewhere with bilateral ARN, was treated, but developed a retinal detachment in the left eye that failed vitrectomy surgery. She was referred 10 years later with recurrent ARN. The infection was difficult to get under control, but eventually responded to intravenous acyclovir and foscarnet. She was given laser photocoagulation. She was placed on oral valacyclovir prophylaxis and was disease-free for 10 years at which point she decided to go to South America on vacation and stop her valacyclovir. Within a few days she developed a recurrence of ARN and flew back for treatment. She had discrete areas of retinal necrosis, vasculitis, and the laser photocoagulation lesions seemed to be ringed by a retinal change suggestive of retinitis. She responded to antiviral treatment, but developed a retinal detachment that was successfully treated. Her visual acuity was 20/20 six years later, and she was using antiviral prophylaxis.
CONCLUSION
Recurrent ARN can respond to aggressive treatment. Chorioretinal scars, such as from photocoagulation, may be potential sites of viral invasion during recurrences. Antiviral prophylaxis may be indicated for at-risk patients.
Topics: Female; Humans; Child, Preschool; Retinal Necrosis Syndrome, Acute; Valacyclovir; Foscarnet; Retinal Detachment; Acyclovir; Antiviral Agents
PubMed: 33346624
DOI: 10.1097/ICB.0000000000001107