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Stem Cells (Dayton, Ohio) Dec 2019Three-dimensional (3D) retinal organoids, in vitro tissue structures derived from self-organizing cultures of differentiating human embryonic stem cells or induced... (Review)
Review
Three-dimensional (3D) retinal organoids, in vitro tissue structures derived from self-organizing cultures of differentiating human embryonic stem cells or induced pluripotent stem cells, could recapitulate some aspects of the cytoarchitectural structure and function of the retina in vivo. 3D retinal organoids display huge potential for the investigation of the pathogenesis of monogenic hereditary eye diseases that are related to the malfunction or degeneration of photoreceptors or retinal ganglion cells by providing an effective in vitro tool with multiple applications. In combination with recent genome editing tools, 3D retinal organoids could also represent a reliable and renewable source of transplantable cells for personalized therapies. In this review, we describe the recent advances in human pluripotent stem cells-derived retinal organoids, determination of their histoarchitecture, complexity, and maturity. We also discuss their application as a means to decipher the pathogenesis of retinal diseases, as well as the main drawbacks and challenges. Stem Cells 2019;37:1496-1504.
Topics: Gene Editing; Induced Pluripotent Stem Cells; Organoids; Retina; Retinal Diseases; Retinal Rod Photoreceptor Cells
PubMed: 31617949
DOI: 10.1002/stem.3089 -
International Ophthalmology Sep 2022To report a series of five cases with retinitis following episodes of febrile illness, its evaluation, management and outcome.
PURPOSE
To report a series of five cases with retinitis following episodes of febrile illness, its evaluation, management and outcome.
METHOD
Retrospective, consecutive case series of five patients presenting with acute retinitis, following a febrile illness.
RESULTS
The retinal lesions had a sudden onset with rapid evolution, preceded by a febrile episode within one month of presentation, in all cases. Extensive serology and PCR testing were non-contributory toward identifying the etiology and guiding therapy. Systemic corticosteroid therapy was effective in hastening the resolution of lesions.
CONCLUSION
Post-fever retinitis appears to be a distinct clinical form of acute hemorrhagic non-necrotizing retinitis without a uniformly identifiable cause, and some evidence pointing toward a para-infectious etiology secondary to flu-like illnesses. With an unusual morphological presentation and annual seasonal patterns in the endemic areas, it is important to differentiate this entity, from other forms of infectious retinitis, before initiating corticosteroid therapy.
Topics: Adrenal Cortex Hormones; Disease Progression; Fever; Humans; Retinitis; Retrospective Studies
PubMed: 35391586
DOI: 10.1007/s10792-022-02258-w -
Eye (London, England) Feb 2022Retinitis pigmentosa is characterized by a dysregulation within the metabolic coupling of the retina, particularly between the glycolytic photoreceptors and the... (Review)
Review
Retinitis pigmentosa is characterized by a dysregulation within the metabolic coupling of the retina, particularly between the glycolytic photoreceptors and the oxidative retina pigment epithelium. This phenomenon of metabolic uncoupling is seen in both aging and retinal degenerative diseases, as well as across a variety of cell types in human biology. Given its crucial role in the health and maintenance of these cell types, the metabolic pathways involved present a suitable area for therapeutic intervention. Herein, this review covers the scope of this delicate metabolic interplay, its dysregulation, how it relates to the retina as well other cell types, and finally concludes with a summary of various strategies aimed at reinstating normal metabolic coupling within the retina, and future directions within the field.
Topics: Humans; Oxidative Stress; Retina; Retinal Degeneration; Retinal Pigment Epithelium; Retinitis Pigmentosa
PubMed: 34974542
DOI: 10.1038/s41433-021-01726-4 -
International Journal of Molecular... Jun 2017Zebrafish are a popular vertebrate model in drug discovery. They produce a large number of small and rapidly-developing embryos. These embryos display rich... (Review)
Review
Zebrafish are a popular vertebrate model in drug discovery. They produce a large number of small and rapidly-developing embryos. These embryos display rich visual-behaviors that can be used to screen drugs for treating retinal degeneration (RD). RD comprises blinding diseases such as Retinitis Pigmentosa, which affects 1 in 4000 people. This disease has no definitive cure, emphasizing an urgency to identify new drugs. In this review, we will discuss advantages, challenges, and research developments in using zebrafish behaviors to screen drugs in vivo. We will specifically discuss a visual-motor response that can potentially expedite discovery of new RD drugs.
Topics: Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Retina; Retinal Degeneration; Vision, Ocular; Zebrafish
PubMed: 28574477
DOI: 10.3390/ijms18061185 -
SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN MACULA-INVOLVING CYTOMEGALOVIRUS RETINITIS.Retina (Philadelphia, Pa.) May 2018To evaluate the microstructural features of cytomegalovirus (CMV) retinitis by spectral domain optical coherence tomography (OCT). (Observational Study)
Observational Study
PURPOSE
To evaluate the microstructural features of cytomegalovirus (CMV) retinitis by spectral domain optical coherence tomography (OCT).
METHODS
Subjects were patients with macula-involving CMV retinitis with OCT imaging. The leading edge of retinitis in the macula was identified based on fundus imaging, and OCT findings were longitudinally evaluated in three areas: within the area of active retinitis, at the leading edge of retinitis, and just beyond the leading edge of retinitis.
RESULTS
Optical coherence tomography imaging of macular CMV retinitis identified vitreous cells in 10 eyes (100%), posterior vitreous detachment in four eyes (40%), broad-based vitreomacular traction in one eye (10%), epiretinal membrane in eight eyes (80%), and lamellar hole-associated epiretinal proliferation associated with an atrophic hole in one eye (10%). Retinal architectural disruption, disruption of inner retinal layers, disruption of the external limiting membrane, and ellipsoid zone abnormalities were noted within the area of retinitis in all eyes and decreased in frequency and severity at and beyond the leading edge of retinitis, although all 10 eyes (100%) exhibited one of these abnormalities, especially outer retinal microabnormalities, beyond the leading edge of retinitis.
CONCLUSION
Microstructural abnormalities were frequently noted on OCT of CMV retinitis, including within the retina beyond the leading edge of retinitis identified by corresponding fundus imaging. Outer retinal abnormalities were noted more frequently than inner retinal abnormalities beyond the leading edge of retinitis. These findings provide insight into the effects of CMV retinitis on retinal microstructure and potentially on vision and highlight the potential utility of OCT for monitoring microprogression of macula-involving CMV retinitis.
Topics: Adult; Cytomegalovirus Retinitis; Disease Progression; Epiretinal Membrane; Female; Fluorescein Angiography; Humans; Macula Lutea; Male; Middle Aged; Retina; Retrospective Studies; Tomography, Optical Coherence; Visual Acuity; Vitreous Body; Young Adult
PubMed: 28376042
DOI: 10.1097/IAE.0000000000001644 -
Scientific Reports Dec 2020To evaluate extralesional microvascular and structural changes of the macula using optical coherence tomography angiography (OCTA) and structural OCT in cytomegalovirus... (Observational Study)
Observational Study
To evaluate extralesional microvascular and structural changes of the macula using optical coherence tomography angiography (OCTA) and structural OCT in cytomegalovirus retinitis (CMVR). An observational study of CMVR patients were performed. Complete ophthalmic examination, serial color fundus photography, structural OCT and OCTA were performed at baseline and follow-up visits for up to 12 months. The structural OCT was analyzed to evaluate macular areas within, bordering and beyond the CMVR lesions. Extralesional retinal capillary plexus of the macula were evaluated by OCT angiography and compared with the unaffected fellow eyes. Thirteen eyes from 13 patients were enrolled. At baseline, macular areas without CMVR lesions showed decreased vessel density (VD) of both the superficial (P = 0.0002) and deep (P < 0.0001) retinal capillary plexus in eyes with CMVR as compared with the corresponding macular areas of the unaffected fellow eyes. The decrease of VD persisted through the follow-up period for up to 12 months after adjusting for degree of vitreous haze. Structural macular OCT characteristics at the borders and beyond the lesions included intraretinal hyperreflective dots, cystoid macular edema, subretinal fluid and selective ellipsoid zone (EZ) loss. The selective EZ loss found in 6 of 12 eyes showed recovery in 4 eyes after receiving anti-viral treatment. In CMVR eyes, there were microvascular and microstructural abnormalities in the macular area without clinically visible CMVR lesions. Our results provided interesting insights into CMV infection of the retina.
Topics: Adult; Cytomegalovirus Retinitis; Female; Fluorescein Angiography; Humans; Macula Lutea; Male; Microvascular Density; Middle Aged; Tomography, Optical Coherence; Young Adult
PubMed: 33293646
DOI: 10.1038/s41598-020-78587-6 -
Stem Cells Translational Medicine Apr 2024Age-related macular degeneration and retinitis pigmentosa are degenerative retinal diseases that cause severe vision loss. Early clinical trials involving... (Review)
Review
Age-related macular degeneration and retinitis pigmentosa are degenerative retinal diseases that cause severe vision loss. Early clinical trials involving transplantation of retinal pigment epithelial cells and/or photoreceptors as a treatment for these conditions are underway. In this review, we summarize recent progress in the field of retinal pigment epithelium transplantation, including some pertinent clinical trial results as well as preclinical studies that address issues of transplant immunology, cell delivery, and cell manufacturing.
Topics: Humans; Retinal Pigment Epithelium; Stem Cell Transplantation; Retinal Diseases; Retina; Macular Degeneration
PubMed: 38394392
DOI: 10.1093/stcltm/szae004 -
Scientific Reports Jul 2018Photoreceptor chromophore, 11-cis retinal (11CR) and the photoproduct, all-trans retinal (ATR), are present in the retina at higher concentrations and interact with the...
Photoreceptor chromophore, 11-cis retinal (11CR) and the photoproduct, all-trans retinal (ATR), are present in the retina at higher concentrations and interact with the visual cells. Non-visual cells in the body are also exposed to retinal that enters the circulation. Although the cornea and the lens of the eye are transparent to the blue light region where retinal can absorb and undergo excitation, the reported phototoxicity in the eye has been assigned to lipophilic non-degradable materials known as lipofuscins, which also includes retinal condensation products. The possibility of blue light excited retinal interacting with cells; intercepting signaling in the presence or absence of light has not been explored. Using live cell imaging and optogenetic signaling control, we uncovered that blue light-excited ATR and 11CR irreversibly change/distort plasma membrane (PM) bound phospholipid; phosphatidylinositol 4,5 bisphosphate (PIP2) and disrupt its function. This distortion in PIP2 was independent of visual or non-visual G-protein coupled receptor activation. The change in PIP2 was followed by an increase in the cytosolic calcium, excessive cell shape change, and cell death. Blue light alone or retinal alone did not perturb PIP2 or elicit cytosolic calcium increase. Our data also suggest that photoexcited retinal-induced PIP2 distortion and subsequent oxidative damage incur in the core of the PM. These findings suggest that retinal exerts light sensitivity to both photoreceptor and non-photoreceptor cells, and intercepts crucial signaling events, altering the cellular fate.
Topics: Animals; Ataxia Telangiectasia Mutated Proteins; Cell Line; HCT116 Cells; HeLa Cells; Humans; Light; Lipofuscin; Mice; NIH 3T3 Cells; Optogenetics; Phosphatidylinositol 4,5-Diphosphate; Photoreceptor Cells, Vertebrate; Retina; Retinaldehyde; Signal Transduction
PubMed: 29976989
DOI: 10.1038/s41598-018-28254-8 -
JAMA Ophthalmology Sep 2014Cytomegalovirus (CMV) retinitis continues to be a leading cause of blindness in many developing countries. Telemedicine holds the potential to increase the number of... (Comparative Study)
Comparative Study
IMPORTANCE
Cytomegalovirus (CMV) retinitis continues to be a leading cause of blindness in many developing countries. Telemedicine holds the potential to increase the number of people screened for CMV retinitis, but it is unclear whether nonophthalmologists could be responsible for interpreting fundus photographs captured in a telemedicine program.
OBJECTIVE
To determine the accuracy of nonophthalmologist photographic graders in diagnosing CMV retinitis from digital fundus photographs.
DESIGN, SETTING, AND PARTICIPANTS
Fifteen nonexpert graders each evaluated 182 mosaic retinal images taken from the eyes of patients with AIDS who were evaluated at the Ocular Infectious Diseases Clinic at Chiang Mai University in Chiang Mai, Thailand.
MAIN OUTCOMES AND MEASURES
Graders diagnosed each image as CMV retinitis present, CMV retinitis absent, or unknown. The results from each grader were compared with those of an indirect ophthalmoscopic examination from an experienced on-site ophthalmologist as well as with the consensus grade given by a panel of CMV retinitis experts.
RESULTS
Relative to the on-site ophthalmologist, the sensitivity of remote CMV retinitis diagnosis by nonexpert graders ranged from 64.0% to 95.5% (mean, 84.1%; 95% CI, 78.6%-89.6%)), and the specificity ranged from 65.6% to 92.5% (mean, 82.3%; 95% CI, 76.6%-88.0%)). Agreement between nonexpert and expert graders was high: the mean sensitivity and specificity values of nonexpert diagnosis using expert consensus as the reference standard were 93.2% (95% CI, 90.6%-95.8%) and 88.4% (95% CI, 85.4%-91.1%), respectively. Mean intrarater reliability also was high (mean Cohen κ, 0.83; 95% CI, 0.78-0.87).
CONCLUSIONS AND RELEVANCE
The sensitivity and specificity of remote diagnosis of CMV retinitis by nonexpert graders was variable, although several nonexperts achieved a level of accuracy comparable to that of CMV retinitis experts. More intensive training and periodic evaluations would be required if nonexperts are to be used in clinical practice.
Topics: AIDS-Related Opportunistic Infections; Allied Health Personnel; Antiviral Agents; Cytomegalovirus Retinitis; Developing Countries; False Positive Reactions; Humans; Male; Middle Aged; Ophthalmology; Ophthalmoscopy; Photography; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Retina; Sensitivity and Specificity; Telemedicine; Thailand; Visual Acuity
PubMed: 24945306
DOI: 10.1001/jamaophthalmol.2014.1108 -
Proceedings of the National Academy of... Nov 2022For sustained vision, photoactivated rhodopsin (Rho*) must undergo hydrolysis and release of all--retinal, producing substrate for the visual cycle and apo-opsin...
For sustained vision, photoactivated rhodopsin (Rho*) must undergo hydrolysis and release of all--retinal, producing substrate for the visual cycle and apo-opsin available for regeneration with 11--retinal. The kinetics of this hydrolysis has yet to be described for rhodopsin in its native membrane environment. We developed a method consisting of simultaneous denaturation and chromophore trapping by isopropanol/borohydride, followed by exhaustive protein digestion, complete extraction, and liquid chromatography-mass spectrometry. Using our method, we tracked Rho* hydrolysis, the subsequent formation of -retinylidene-phosphatidylethanolamine (-ret-PE) adducts with the released all--retinal, and the reduction of all--retinal to all--retinol. We found that hydrolysis occurred faster in native membranes than in detergent micelles typically used to study membrane proteins. The activation energy of the hydrolysis in native membranes was determined to be 17.7 ± 2.4 kcal/mol. Our data support the interpretation that metarhodopsin II, the signaling state of rhodopsin, is the primary species undergoing hydrolysis and release of its all--retinal. In the absence of NADPH, free all--retinal reacts with phosphatidylethanolamine (PE), forming a substantial amount of -ret-PE (∼40% of total all--retinal at physiological pH), at a rate that is an order of magnitude faster than Rho* hydrolysis. However, -ret-PE formation was highly attenuated by NADPH-dependent reduction of all--retinal to all--retinol. Neither -ret-PE formation nor all--retinal reduction affected the rate of hydrolysis of Rho*. Our study provides a comprehensive picture of the hydrolysis of Rho* and the release of all--retinal and its reentry into the visual cycle, a process in which alteration can lead to severe retinopathies.
Topics: Rhodopsin; Retinaldehyde; Vitamin A; Hydrolysis; NADP
PubMed: 36322748
DOI: 10.1073/pnas.2213911119