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Cellular Signalling May 2020The chemical- and photo- toxicity of chromophore retinal on cells have long been debated. Although we recently showed that retinal and blue light exposure interrupt...
The chemical- and photo- toxicity of chromophore retinal on cells have long been debated. Although we recently showed that retinal and blue light exposure interrupt cellular signaling, a comprehensive study examining molecular underpinnings of this perturbation and its consequences to cellular fate is lacking. Here, we report molecular evidence for blue light excited-retinal induced oxidative damage of polyunsaturated lipid anchors in membrane-interacting signaling molecules and DNA damage in cells using live-cell imaging and in vitro experimentation. The incurred molecular damage irreversibly disrupted subcellular localization of these molecules, a crucial criterion for their signaling. We further show retinal accumulation in lipid-bilayers of cell membranes could enhance the lifetime of retinal in cells. Comparative response-signatures suggest that retinal triggers reactions upon photoexcitation similar to photodynamic therapy agents and generate reactive oxygen species in cells. Additionally, data also shows that exposing retinal-containing cells to sunlight induces substantial cytotoxicity. Collectively, our results explain a likely in vivo mechanism and reaction conditions under which bio-available retinal in physiological light conditions damages cells.
Topics: DNA Damage; HeLa Cells; Humans; Light; Lipid Peroxidation; Oxidative Stress; Photochemical Processes; Reactive Oxygen Species; Retinaldehyde
PubMed: 31982549
DOI: 10.1016/j.cellsig.2020.109547 -
Medicina 2023
Topics: Humans; Cryptococcosis; Retinitis; Antifungal Agents
PubMed: 38117731
DOI: No ID Found -
Investigative Ophthalmology & Visual... Apr 2016The recent advances in cell-based therapies for the repair of the pigmented epithelium is providing additional impetus for the translation of photoreceptor... (Review)
Review
The recent advances in cell-based therapies for the repair of the pigmented epithelium is providing additional impetus for the translation of photoreceptor transplantation to eventual clinical trials. The prospects for transplantation of photoreceptors as a potential therapy for the treatment of photoreceptor degeneration will depend on successfully addressing many critical issues in preclinical studies. Although most of the studies that have carried out transplants of photoreceptors have primarily used normal mice, there have been recent reports that have also shown some success following transplantation to mouse models of retinitis pigmentosa. However, while these results are promising, there are several key issues that require further investigation in order to better understand the optimum timing for transplantation, given the extensive remodeling of the retina that occurs in late stage disease.
Topics: Animals; Cell Transplantation; Disease Models, Animal; Mice; Photoreceptor Cells, Vertebrate; Retina; Retinal Degeneration
PubMed: 27116664
DOI: 10.1167/iovs.15-17659 -
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 -
Experimental Biology and Medicine... Jul 2020As the center of phototransduction, retinal photoreceptors are responsible for capturing and converting photon energy to bioelectric signals for following visual... (Review)
Review
As the center of phototransduction, retinal photoreceptors are responsible for capturing and converting photon energy to bioelectric signals for following visual information processing in the retina. This article summarizes experimental observation and discusses biophysical mechanism of fast photoreceptor-intrinsic optical signal (IOS) correlated with early phase of phototransduction. Quantitative imaging of fast photoreceptor-IOS may provide objective optoretinography to advance the study and diagnosis of age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and other eye diseases that can cause photoreceptor dysfunctions.
Topics: Female; Humans; Light Signal Transduction; Photoreceptor Cells, Vertebrate; Retina; Retinitis Pigmentosa; Tomography, Optical Coherence
PubMed: 32558598
DOI: 10.1177/1535370220935406 -
Frontiers in Cellular and Infection... 2023Cytomegalovirus retinitis (CMVR) is the most common and sight-threatening opportunistic retinal infection in patients with acquired immunodeficiency syndrome (AIDS) and...
BACKGROUND
Cytomegalovirus retinitis (CMVR) is the most common and sight-threatening opportunistic retinal infection in patients with acquired immunodeficiency syndrome (AIDS) and several controversies remain to be settled. We aimed to summarize the current evidence and clarify the clinical features and prognosis of CMVR in AIDS patients.
METHODS
The databases PubMed, EMBASE, and Ovid from inception to April 2022 were searched to identify the relevant studies. R software version 3.6.3 was used to perform the statistical analyses. Results in proportion with 95% confidence interval (CI) were calculated using the Freeman-Tukey variant of arcsine square transformation.
RESULTS
We finally included 236 studies comprising 20,214 patients. CMVR in AIDS was male-dominated (88%, 95%CI 86%-89%), with 57% (95%CI 55%-60%) aged <41 years and 44% (95%CI 41%-47%) being bilaterally involved. CMVR was preponderant in AIDS patients with the following characteristics: white and non-Hispanic, homosexual, HIV RNA load ≥ 400 copies/mL, and CD4+ T-cells <50 cells/μL. The positivity of CMV-DNA in blood, aqueous humor, and vitreous humor was 66% (95%CI 52%-79%), 87% (95%CI 76%-96%), and 95% (95%CI 85%-100%), respectively. The most common symptoms were blurred vision (55%, 95%CI 46%-65%), followed by asymptomatic, visual field defect, and floaters. CMVR was first diagnosed and regarded as the clue to AIDS diagnosis in 9% (95%CI 6%-13%) of CMVR patients. Approximately 85% (95%CI 76%-93%) of the CMVR patients have received cART. CMVR remission was observed in 72%-92% of patients depending on the specific category of anti-CMV therapy. The general incidence of CMVR-related RD in the entire course was 24% (95%CI 18%-29%), of which most patients received PPV with SO or gas tamponade and the rate of anatomic success was 89% (95%CI 85%-93%).
CONCLUSION
CMVR is a common opportunistic infection with diverse clinical features in AIDS patients, preponderant in those who are male, homosexual, or with CD4+ T-cells <50 cells/μL. Current therapies for CMVR and CMVR-related RD were shown to be effective. Early detection and routine ophthalmic screening should be promoted in AIDS patients.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42022363105.
Topics: Humans; Male; Female; Cytomegalovirus Retinitis; Acquired Immunodeficiency Syndrome; Opportunistic Infections; CD4-Positive T-Lymphocytes; Retina
PubMed: 37305416
DOI: 10.3389/fcimb.2023.1107237 -
Jornal Brasileiro de Nefrologia 2022Cytomegalovirus (CMV) retinitis is a rare manifestation of CMV invasive disease and potentially threatening to vision in immunocompromised individuals. Clinical...
Cytomegalovirus (CMV) retinitis is a rare manifestation of CMV invasive disease and potentially threatening to vision in immunocompromised individuals. Clinical suspicion is fundamental since it is an unusual entity with a progressive and often asymptomatic installation over a long period. The authors report a 70-year-old man with diabetic nephropathy who underwent a kidney transplant (KT) in August 2014 with good clinical evolution. No previous CMV infection or episodes of acute rejection were reported. Five years after transplant, he was admitted due to a reduced visual acuity of the left eye with seven days of evolution with associated hyperemia, without exudate. The ophthalmologic evaluation was compatible with acute necrosis of the retina and presumed associated with CMV infection. He had a progressive improvement after ganciclovir initiation. CMV retinitis is one of the most serious ocular complications in immune-suppressed individuals and can lead to irreversible blindness, and because of that, early diagnosis and treatment remains crucial in obtaining the best visual prognosis in affected patients. Secondary prophylaxis with ganciclovir is not consensual, neither is the safety of reintroducing the antimetabolite in these cases.
Topics: Aged; Antimetabolites; Antiviral Agents; Cytomegalovirus Retinitis; Ganciclovir; Humans; Kidney Transplantation; Male
PubMed: 33973995
DOI: 10.1590/2175-8239-JBN-2020-0254 -
Scientific Reports May 2021Free fatty acid dysregulation in diabetics may elicit the release of inflammatory cytokines from Müller cells (MC), promoting the onset and progression of diabetic...
Free fatty acid dysregulation in diabetics may elicit the release of inflammatory cytokines from Müller cells (MC), promoting the onset and progression of diabetic retinopathy (DR). Palmitic acid (PA) is elevated in the sera of diabetics and stimulates the production of the DR-relevant cytokines by MC, including IL-1β, which induces the production of itself and other inflammatory cytokines in the retina as well. In this study we propose that experimental elevation of cytochrome P450 epoxygenase (CYP)-derived epoxygenated fatty acids, epoxyeicosatrienoic acid (EET) and epoxydocosapentaenoic acid (EDP), will reduce PA- and IL-1β-induced MC inflammation. Broad-spectrum CYP inhibition by SKF-525a increased MC expression of inflammatory cytokines. Exogenous 11,12-EET and 19,20-EDP significantly decreased PA- and IL-1β-induced MC expression of IL-1β and IL-6. Both epoxygenated fatty acids significantly decreased IL-8 expression in IL-1β-induced MC and TNFα in PA-induced MC. Interestingly, 11,12-EET and 19,20-EDP significantly increased TNFα in IL-1β-treated MC. GSK2256294, a soluble epoxide hydrolase (sEH) inhibitor, significantly reduced PA- and IL-1β-stimulated MC cytokine expression. 11,12-EET and 19,20-EDP were also found to decrease PA- and IL-1β-induced NFκB-dependent transcriptional activity. These data suggest that experimental elevation of 11,12-EET and 19,20-EDP decreases MC inflammation in part by blocking NFκB-dependent transcription and may represent a viable therapeutic strategy for inhibition of early retinal inflammation in DR.
Topics: Cells, Cultured; Cyclohexylamines; Cytochrome P-450 Enzyme System; Diabetic Retinopathy; Ependymoglial Cells; Epoxide Hydrolases; Fatty Acids; Humans; Inflammation Mediators; NF-kappa B; Neuroglia; Promoter Regions, Genetic; Retinitis; Triazines
PubMed: 33958662
DOI: 10.1038/s41598-021-89000-1 -
Cells Jun 2023Retinal degenerative diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa, lack effective therapies. Conventional monotherapeutic...
Retinal degenerative diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa, lack effective therapies. Conventional monotherapeutic approaches fail to target the multiple affected pathways in retinal degeneration. However, the retinal pigment epithelium (RPE) secretes several neurotrophic factors addressing diverse cellular pathways, potentially preserving photoreceptors. This study explored human embryonic stem cell-derived, polarized RPE soluble factors (PRPE-SF) as a combination treatment for retinal degeneration. PRPE-SF promoted retinal progenitor cell survival, reduced oxidative stress in ARPE-19 cells, and demonstrated critical antioxidant and anti-inflammatory effects for preventing retinal degeneration in the Royal College of Surgeons (RCS) rat model. Importantly, PRPE-SF treatment preserved retinal structure and scotopic b-wave amplitudes, suggesting therapeutic potential for delaying retinal degeneration. PRPE-SF is uniquely produced using biomimetic membranes for RPE polarization and maturation, promoting a protective RPE secretome phenotype. Additionally, PRPE-SF is produced without animal serum to avoid immunogenicity in future clinical development. Lastly, PRPE-SF is a combination of neurotrophic factors, potentially ameliorating multiple dysfunctions in retinal degenerations. In conclusion, PRPE-SF offers a promising therapeutic candidate for retinal degenerative diseases, advancing the development of effective therapeutic strategies for these debilitating conditions.
Topics: Rats; Humans; Animals; Retinal Pigment Epithelium; Retinal Degeneration; Secretome; Retina; Photoreceptor Cells
PubMed: 37443724
DOI: 10.3390/cells12131689 -
BMC Ophthalmology Aug 2023Cat-scratch disease typically presents with various ocular manifestations such as uveitis, vitritis, retinitis, retinochoroiditis, and optic neuritis. However, fundus...
BACKGROUND
Cat-scratch disease typically presents with various ocular manifestations such as uveitis, vitritis, retinitis, retinochoroiditis, and optic neuritis. However, fundus nodular lesions was rarely reported. In our study, we reported a case of Cat-Scratch disease with binocular fundus nodular lesions.
CASE PRESENTATION
An 11-year old male presented with uveitis in the right eye and bilateral fundus nodular lesions after indirect contact with unvaccinated cats. Comprehensive ancillary examinations including wide-angle fundus photography, ultrasonography, fluorescein fundus angiography, optical coherence tomography, and orbital magnetic resonance imaging were performed to elucidate the multidimensional features of the binocular lesions. Metagenomics next-generation sequencing was utilized to confirm the diagnosis of Cat-scratch disease. The patient's condition showed improvement after a 6-month combination treatment regimen involving systemic administration of doxycycline hyclate and methylprednisolone tablets, as well as local application of mydriatic and corticosteroid eye drops.
CONCLUSIONS
We firstly reported a case of Cat-scratch disease presenting simultaneously with uveitis and fundus nodular lesions caused by Bartonella henselae infection in a child. Timely diagnosis and treatment with antibiotics and corticosteroids showed promising outcomes for the prognosis of these ocular disorders.
Topics: Male; Humans; Cat-Scratch Disease; Bartonella henselae; Fundus Oculi; Retinitis; Chorioretinitis
PubMed: 37544996
DOI: 10.1186/s12886-023-03063-4