Tazbir Ahmed

All Publications

• Axonal Energy Crisis and Calcium Phosphate Dysregulation as Pathogenesis of Optic Disc Drusen. Aging and disease Modgil, S., Ahmed, T., Liao, Y. J. 2024

  Abstract

  Soft tissue ectopic calcification is due to abnormal accumulation of calcium and phosphate outside the bone. It is the result of the failure of a complex, active, and highly regulated process - much of which is still not well understood. Some of our understanding of ectopic calcification come from studies on diseases such as atherosclerosis, aortic valve disease and kidney stone disease. In the eye, the most common causes of visual defects due to ectopic calcification include optic disc drusen (ODD) and age-related macular degeneration (AMD). In ODD, ectopic calcification occurs only in the most anterior, unmyelinated portion of optic nerve - the sole output of the eye and particularly susceptible to hypoxic and metabolic stress. In this article, we review the effects of hypoxia on mitochondrial function and calcium regulation and delineate the key processes likely involved in ectopic calcification. We propose a working hypothesis for ODD centering on the role of hypoxia-induced calcium and phosphate overload, mitochondrial dysfunction and osteogenic differentiation, leading to hydroxyapatite deposition and biomineralization.

  View details for DOI 10.14336/AD.2024.0459

  View details for PubMedID 39500350

• Roles of Sphingosine Kinase and Sphingosine-1-Phosphate Receptor 2 in Endotoxin-Induced Acute Retinal Inflammation. Ocular immunology and inflammation Ahmed, T., Suzuki, T., Terao, R., Yamagishi, R., Fujino, R., Azuma, K., Soga, H., Ueta, T., Honjo, M., Watanabe, S., Yoshioka, K., Takuwa, Y., Aihara, M. 2023: 1-15

  Abstract

  PURPOSE: To investigate the roles of sphingosine kinases (SphKs) and sphingosine-1-phosphate receptors (S1PRs) in endotoxin-induced uveitis (EIU) mice.METHODS: EIU model was induced using an intraperitoneal injection of lipopolysaccharide (LPS). The expression of SphKs and S1PRs in the retina was assessed using quantitative polymerase chain reaction (qPCR) and immunofluorescence. The effects of S1PR antagonists on the expression of inflammatory cytokines in the retina were evaluated using qPCR and western blotting. Effects of leukocyte infiltration of the retinal vessels were evaluated to determine the effects of the S1PR2 antagonist and genetic deletion of S1PR2 on retinal inflammation.RESULTS: Retinal SphK1 expression was significantly upregulated in EIU. SphK1 was expressed in the GCL, IPL, and OPL and S1PR2 was expressed in the GCL, INL, and OPL. Positive cells in IPL and OPL of EIU retina were identified as endothelial cells. S1PR2 antagonist and genetic deletion of S1PR2 significantly suppressed the expression of IL-1alpha, IL-6, TNF-alpha, and ICAM-1, whereas S1PR1/3 antagonist did not. Use of S1PR2 antagonist and S1PR2 knockout in mice significantly ameliorated leukocyte adhesion induced by LPS.CONCLUSION: SphK1/S1P/S1PR2 signaling was upregulated in EIU and S1PR2 inhibition suppressed inflammatory response. Targeting this signaling pathway has potential for treating retinal inflammatory diseases.

  View details for DOI 10.1080/09273948.2023.2273963

  View details for PubMedID 38100527

• Oxidative Stress-Induced Cellular Senescence in Aging Retina and Age-Related Macular Degeneration. Antioxidants (Basel, Switzerland) Terao, R., Ahmed, T., Suzumura, A., Terasaki, H. 2022; 11 (11)

  Abstract

  Aging leads to a gradual decline of function in multiple organs. Cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) are age-related ocular diseases. Because their pathogenesis is unclear, it is challenging to combat age-related diseases. Cellular senescence is a cellular response characterized by cell cycle arrest. Cellular senescence is an important contributor to aging and age-related diseases through the alteration of cellular function and the secretion of senescence-associated secretory phenotypes. As a driver of stress-induced premature senescence, oxidative stress triggers cellular senescence and age-related diseases by inducing senescence markers via reactive oxygen species and mitochondrial dysfunction. In this review, we focused on the mechanism of oxidative stress-induced senescence in retinal cells and its role in the pathogenesis of AMD.

  View details for DOI 10.3390/antiox11112189

  View details for PubMedID 36358561

  View details for PubMedCentralID PMC9686487

• Long-term results of the safety and effectiveness of a novel microshunt in Japanese patients with primary open-angle glaucoma. Japanese journal of ophthalmology Ahmed, T., Honjo, M., Sakata, R., Fujishiro, T., Shirato, S., Aihara, M. 2022; 66 (1): 33-40

  Abstract

  To evaluate the long-term safety and effectiveness of the Preserflo MicroShunt in Japanese primary open-angle glaucoma (POAG) patients.Single-site, nonrandomized observational study.Eight eyes of 7 POAG patients were included. The surgical complications and interventions were monitored. The preoperative and postoperative intraocular pressures (IOPs), numbers of antiglaucoma medications, logarithm of the minimum angle of resolution visual acuity (VA), mean deviation (MD) slope, and corneal endothelial cell density (CECD) were compared retrospectively.The mean follow-up period was 68.9 months (range, 48-76 months). The baseline IOP of 17.9 ± 3.5 mmHg and the number of glaucoma medications of 3.5 ± 0.5 were significantly reduced at subsequent follow-up visits. At 1, 2, 3, 4, 5, and 6 years postoperatively, the IOPs were 13.8 ± 2.9, 12.8 ± 2.3, 12.1 ± 3.2, 12.6 ± 2.5, 12.3 ± 1.0, and 13.5 ± 3.1 mmHg, respectively, with the use of 1.6 ± 1.4, 1.6 ± 1.6, 1.5 ± 1.4, 1.5 ± 1.4, 1.9 ± 1.3, and 2.0 ± 1.1 medications. Postoperative transient hyphema occurred in 1 eye. Postoperative needling was required in 5 eyes, 12 times in total. No eyes showed significant VA decline, except for 1 eye with a severe central visual field defect that existed preoperatively. The preoperative MD slope of - 1.6 ± 1.2 dB/year improved significantly, to - 0.3 ± 0.2 dB/year (P = 0.023), postoperatively. The baseline CECD decreased from 2595 ± 292 to 2478.4 ± 255 postoperatively.The microshunt surgical procedure is safe and effective for Japanese POAG patients.

  View details for DOI 10.1007/s10384-021-00893-x

  View details for PubMedID 34988757

• Cytokine profiles in the aqueous humor following brolucizumab administration for exudative age-related macular degeneration GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY Terao, R., Obata, R., Okubo, A., Aoki, S., Azuma, K., Ahmed, T., Inoda, S., Hashimoto, Y., Takahashi, R., Yoshida, H., Misawa, M., Takahashi, H., Takahashi, H. 2023

  Abstract

  To identify the inflammatory cytokine profile in the aqueous humor (AH) of patients with intraocular inflammation (IOI) after intravitreal administration of brolucizumab (IVBr) for neovascular age-related macular degeneration.Eight eyes from seven patients with IOI after initial IVBr (IVBrIOI +) were enrolled. Sixteen eyes from 16 patients without IOI after IVBr (IVBrIOI -) and aflibercept (IVA) were used as controls. AH samples were analyzed using a multiplex immunoassay.C-C motif chemokine ligand (CCL)2, C-X-C motif chemokine ligand (CXCL)1, CXCL10, CXCL13, interleukin (IL)-6, IL-8, IL-10, matrix metalloproteinase (MMP)-1, MMP-9, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), intercellular adhesion molecule (ICAM)-1, E-selectin, and P-selectin levels were significantly higher in IVBrIOI + than in IVBrIOI - and IVA. Vascular endothelial growth factor (VEGF) was significantly lower in IVBrIOI - compared to that in IVBrIOI + and IVA. In the IVBrIOI + group, there were significant correlations between CCL2, CXCL1, IL-6, IL-8, IL-10, G-CSF, GM-CSF, ICAM-1, and E-selectin, which also exhibited significant correlations in the IVBrIOI - group.The number of inflammatory cytokines increases during IOI, which is associated with type IV hypersensitivity and vascular inflammation. Some cytokines exhibit correlations even in non-inflamed eyes, indicating a subclinical response to IVBr.

  View details for DOI 10.1007/s00417-023-06038-9

  View details for Web of Science ID 000960769100002

  View details for PubMedID 37000271

  View details for PubMedCentralID 9369215

• Risk Factors and Treatment Strategy for Retinal Vascular Occlusive Diseases. Journal of clinical medicine Terao, R., Fujino, R., Ahmed, T. 2022; 11 (21)

  Abstract

  Retinal occlusive diseases are common diseases that can lead to visual impairment. Retinal artery occlusion and retinal vein occlusion are included in the clinical entity, but they have quite different pathophysiologies. Retinal artery occlusion is an emergent eye disorder. Retinal artery occlusion is mainly caused by thromboembolism, which frequently occurs in conjunction with life-threatening stroke and cardiovascular diseases. Therefore, prompt examinations and interventions for systemic vascular diseases are often necessary for these patients. Retinal vein occlusion is characterized by retinal hemorrhage and ischemia, which may impair visual function via several complications such as macular edema, macular ischemia, vitreous hemorrhage, and neovascular glaucoma. Even though anti-vascular endothelial growth factor therapy is the current established first-line of treatment for retinal vein occlusion, several clinical studies have been performed to identify better treatment protocols and new therapeutic options. In this review, we summarize the current findings and advances in knowledge regarding retinal occlusive diseases, particularly focusing on recent studies, in order to provide an update for a better understanding of its pathogenesis.

  View details for DOI 10.3390/jcm11216340

  View details for PubMedID 36362567

  View details for PubMedCentralID PMC9656338