ArticleInvestigative ophthalmology & visual science2016
Photoreceptor Cells Produce Inflammatory Mediators That Contribute to Endothelial Cell Death in Diabetes.
Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 79 citations in OpenAlex.
- Retinal Capillary Loss Is More Severe in the Midperiphery Than in the Macula in Eyes With Diabetic Retinopathy Compared to Healthy Eyes.Translational vision science & technology · 2026Article
- Baseline Deep Capillary Plexus Ischemia Predicts Earlier Diabetic Retinopathy Complications Than Foveal Avascular Enlargement.American journal of ophthalmology · 2026Article
- The positive correlation between the progressive photoreceptor damage and the increased macular leakage indicating the severity of diabetic retinopathy.Journal of diabetes investigation · 2026Article
- Macular Microaneurysms Are Associated With Chronic Kidney Disease and Deep Capillary Plexus Ischemia in Referable Diabetic Retinopathy.Investigative ophthalmology & visual science · 2025Article
- Macular Deep Capillary Plexus Ischemia as a Biomarker for Identifying Referable Diabetic Retinopathy.Investigative ophthalmology & visual science · 2025Article
- The Importance of Matching Optical Coherence Tomography Angiography Metrics to Diabetic Retinopathy Severity for Detecting Progression.Investigative ophthalmology & visual science · 2025Observational
- Optical coherence tomography angiography in non-alcoholic fatty liver disease: is it a disease affecting the microvascular system??BMC ophthalmology · 2025Article
- Volumetric Measures of Capillary Nonperfusion on Optical Coherence Tomography Angiography Detect Early Ischemia in Diabetes Without Retinopathy.Investigative ophthalmology & visual science · 2025Article
- The Exploration of Disturbance of Capillary and Photoreceptor Communication Networks in Diabetic Retinopathy Through Single-Cell RNA-Seq.Journal of cellular and molecular medicine · 2025Article
- Breach and restoration of retinal immune privilege: barrier failure, innate dysregulation, and adaptive autoimmunity.Frontiers in immunology · 2025Review
- Clinical metabolomics in type 2 diabetes mellitus: from pathogenesis to biomarkers.Frontiers in endocrinology · 2025Review
- Quantification of Photoreceptors' Changes in a Diabetic Retinopathy Model with Two-Photon Imaging Microscopy.International journal of molecular sciences · 2024Article
- Metformin and Glucose Concentration as Limiting Factors in Retinal Pigment Epithelial Cell Viability and Proliferation.International journal of molecular sciences · 2024Article
- Cell and molecular targeted therapies for diabetic retinopathy.Frontiers in endocrinology · 2024Review
- Ocular Vascular Diseases: From Retinal Immune Privilege to Inflammation.International journal of molecular sciences · 2023Review
- Retinal Cell Damage in Diabetic Retinopathy.Cells · 2023Review
- Elucidating glial responses to products of diabetes-associated systemic dyshomeostasis.Progress in retinal and eye research · 2023Review
- Evaluation of Photobiomodulation and Boldine as Alternative Treatment Options in Two Diabetic Retinopathy Models.International journal of molecular sciences · 2023Article
- Deep Capillary Nonperfusion on OCT Angiography Predicts Complications in Eyes with Referable Nonproliferative Diabetic Retinopathy.Ophthalmology. Retina · 2023Observational
- Proteomic Profiling Revealed Mitochondrial Dysfunction in Photoreceptor Cells under Hyperglycemia.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
purposeRecent studies suggest that photoreceptor cells regulate local inflammation in the retina in diabetes. The purpose of this study was to determine if photoreceptor cells themselves produce inflammatory proteins in diabetes and if soluble factors released by photoreceptors in elevated glucose induce inflammatory changes in nearby cells.
methodsLaser capture microdissection was used to isolate the outer retina (photoreceptors) from the inner retina in nondiabetic and diabetic mice. Diabetes-induced changes in the expression of inflammatory targets were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. Cell culture experiments were carried out to determine if photoreceptors in vitro and ex vivo release soluble mediators that can stimulate nearby cells. Photoreceptor contribution to leukocyte-mediated endothelial cell death was tested using coculture models.
resultsMessenger ribonucleic acid and protein expression levels for inflammatory proteins intercellular adhesion molecule 1 (ICAM1), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX2) were increased in photoreceptors cells in diabetes. In vitro and ex vivo studies show that photoreceptor cells in elevated glucose release mediators that can induce tumor necrosis factor-α in leukocytes and endothelial cells, but not in glia. The soluble mediators released by photoreceptor cells in elevated glucose are regulated by transforming growth factor β-activated kinase 1 and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) signaling. In contrast to enhanced leukocyte-mediated killing of endothelial cells by leukocytes from wild-type diabetic mice, leukocytes from diabetic mice lacking photoreceptor cells (opsin-/-) did not kill endothelial cells.
conclusionsThese data indicate that photoreceptor cells are a source of inflammatory proteins in diabetes, and their release of soluble mediators can contribute to the death of retinal capillaries in diabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.