Journals / Turkish Journal of Medical Sciences / 2020 / Cilt: 50 - Sayı: 4

Ocular toxicity of intravitreal golimumab in a rabbit model

Pages
1111–1122
Publication Date
2020-08-01
DOI
—
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Potential retinal toxicity of intravitreal golimumab should be considered if an intravitreal administration is planned.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Background/aim: To investigate the effect of intravitreal golimumab on rabbit retina histopathology.
📊
Key Findings & Data:The right eye of each rabbit in groups I, II, and III received a single intravitreal injection of 5 mg/0.05 mL 6 eyes , 10 mg/0.1 mL 6 eyes , or 20 mg/0.2 mL 4 eyes golimumab, while left eyes served as controls with the same volume of a balanced salt solution injection.
💡
Conclusion & Impact:Potential retinal toxicity of intravitreal golimumab should be considered if an intravitreal administration is planned.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Apoptosis · golimumab · intravitreal anti-TNF drugs

Abstract

Background/aim: To investigate the effect of intravitreal golimumab on rabbit retina histopathology. Materials and methods: Sixteen albino New Zealand rabbits were divided into three groups. The right eye of each rabbit in groups I, II, and III received a single intravitreal injection of 5 mg/0.05 mL 6 eyes , 10 mg/0.1 mL 6 eyes , or 20 mg/0.2 mL 4 eyes golimumab, while left eyes served as controls with the same volume of a balanced salt solution injection. All animals were examined using slit-lamp biomicroscopy and indirect ophthalmoscopy before and after intravitreal injection and at days 1 and 7. Animals were euthanized on day 7 and the eyes were enucleated for immunohistochemistry evaluation and electron microscopic examination of the retinas. Results: For groups I, II, and III, the number of cells in the outer nuclear layer and the inner nuclear layer was decreased compared to those in the control groups. In group I, the percentage of caspase-3 staining of the outer nuclear layer was significantly higher than that in the control. For groups II and III, TUNEL and caspase-3 staining percentages in the outer and inner nuclear layers were found to be significantly higher than those for the control groups. In the ganglion cell layer, for groups I, II, and III, neither TUNEL nor caspase-3 staining percentages showed any significant difference between two groups. No significant dose-dependent relationship was found for increasing doses of golimumab in all layers. Myelin figures and karyorrhexis in the photoreceptor cells were prominent in electron microscopy of the golimumab-injected eyes. Conclusion: Golimumab caused apoptosis in both photoreceptors and bipolar cells of the rabbit retina. Potential retinal toxicity of intravitreal golimumab should be considered if an intravitreal administration is planned.

🔖

Cite This Article

ENGİN, C. D., MIÇILI, S. C., YILMAZ, O., BAĞRIYANIK, H. A., ERGÜR, B. U., ÖNEN, F., SAATCİ, A. O. (2020). Ocular toxicity of intravitreal golimumab in a rabbit model. Turkish Journal of Medical Sciences, Cilt: 50 - Sayı: 4, 1111–1122. https://ajindex.com/articles/113199

References (13)

  1. Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 2001; 104 (4): 487-501
  2. Myśliwiec M, Balcerska A, Zorena K, Myśliwska J, Lipowski P et al. The role of vascular endothelial growth factor, tumor necrosis factor alpha and interleukin-6 in pathogenesis of diabetic retinopathy. Diabetes Research and Clinical Practice 2008; 79 (1): 141-146
  3. Santos Lacomba M, Marcos Martín C, Gallardo Galera JM, Gómez Vidal MA, Collantes Estévez E et al. Aqueous humor and serum tumor necrosis factor-alpha in clinical uveitis. Ophthalmic Research 2001; 33 (5): 251-255
  4. Takase H, Futagami Y, Yoshida T, Kamoi K, Sugita S et al. Cytokine profile in aqueous humor and sera of patients with infectious or noninfectious uveitis. Investigative Ophthalmology & Visual Science 2006; 47 (4): 1557-1561
  5. Nita M, Grzybowski A. The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxidative Medicine and Cellular Longevity 2016; 2016: 3164734
  6. Feldmann M, Maini RN. Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? The Annual Review of Immunology 2001; 19: 163-196
  7. Reiff A. Long-term outcome of etanercept therapy in children with treatment-refractory uveitis. Arthritis & Rheumatology 2003; 48 (7): 2079-2080
  8. Takeuchi M, Kezuka T, Sugita S, Keino H, Namba K et al. Evaluation of the long-term efficacy and safety of infliximab treatment for uveitis in Behçet’s disease: A multicenter study. Ophthalmology 2014; 121 (10): 1877-1884
  9. Interlandi E, Leccese P, Olivieri I, Latanza L. Adalimumab for treatment of severe Behcet’s uveitis: a retrospective long-term follow-up study. Clinical and Experimental Rheumatology 2014; 32 (4 Suppl 84): S58-62
  10. Mirshahi A, Hoehn R, Lorenz K, Kramann C, Baatz H. Antitumor necrosis factor alpha for retinal diseases: current knowledge and future concepts. Journal of Ophthalmic and Vision Research 2012; 7 (1): 39-44
  11. Giganti M, Beer PM, Lemanski N, Hartman C, Schartman J et al. Adverse events after intravitreal infliximab (Remicade). Retina 2010; 30 (1): 71-80
  12. Markomichelakis N, Delicha E, Masselos S, Sfikakis PP. Intravitreal infliximab for sight-threatening relapsing uveitis in Behçet disease: A pilot study in 15 patients. American Journal of Ophthalmology 2012; 154 (3): 534-541
  13. Tsilimbaris MK, Panagiotoglou TD,