{"title":"玻璃体内抗tnf - alfa对实验性兔青光眼模型的神经炎症控制和神经保护作用","authors":"Okyanus Bulut Tarlabolen, Mine Esen Baris, Emrah Soylu, Banu Yaman, Timur Kose, Suzan Guvenyilmaz","doi":"10.1111/aos.17102","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <p><b>Aims/Purpose:</b> The aim of the study is to create a microbead induced ocular hypertension (OHT) model in rabbits, and to evaluate the effects of intravitreal and intraperitoneal injections of Adalimumab (ADA) on the number of retinal ganglion cells (RGC), retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness.</p>\n \n <p><b>Methods:</b> 15 rabbits of mixed strain (9–12 months old, 3.5-4kg) were randomized into 4 groups. OHT was induced with microbead injection into the anterior chamber of right eyes. On 7th, 14th days of OHT, ADA was injected at one of two concentrations (2.5mg group 1: G1/5mg group 2:G2) into right eyes of two groups, intraperitoneally 5mg/kg into the third group (G3), and balanced salt solution into fourth group (sham). The left eyes were used as controls. At 40<sup>th</sup> day, the rabbits were euthanized. Retinal and optic nerve head (ONH) histology was studied with hematoxylin-eosin and toluidine blue staining.</p>\n \n <p><b>Results:</b> OHT was induced with microbeads in 13 eyes. 2 rabbits were excluded (endophthalmitis, total hyphema). The average pre-OHT IOP from all eyes 9.7±09mmHg (8-11). Statistically significant IOP increase was observed in all subject eyes on day 7 (14±1.4 (12-18)) (<i>p</i> = 0.01) and maintained until ADA injection (day 21). RGCs in the eyes with elevated IOP were 7.2±1.2 and 7.6±1.5, 6.3+1.1 cells in ADA treated groups, G1, G2, G3, respectively. There was no statistically significant difference between treatment groups. The average RNFL was 125.9±10.9 μm in control, 60.2±9.4 μm in G1, 45.7±2.9 μm in G2, 22.8±2.9 μm in G3, 21.7±10 μm in sham. Significant elevation was observed in G1 compared to all treatment groups. (<i>p</i> = 0.01). The average GCC of control was 45.5±1.9 μm, G1 41.2±2.2 μm, G2 39.3±3.3 μm, G3 34.1±1.6 μm, sham was 38.3±1.1 μm. Significant increase was observed in G1 compared to G3. (<i>p</i> = 0.01).</p>\n \n <p><b>Conclusions:</b> OHT triggers inflammatory response in which TNF-α expression is increased around the ONH. Blocking TNF-α might prevent axonal degeneration and RGC loss by inhibiting this response. These findings may further contribute to the literature for a new treatment strategy for glaucoma using TNF-α antagonists or inflammation suppressors.</p>\n </section>\n </div>","PeriodicalId":6915,"journal":{"name":"Acta Ophthalmologica","volume":"103 S284","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/10.1111/aos.17102","citationCount":"0","resultStr":"{\"title\":\"Effectiveness of intravitreal antitNF-ALFA for neuroinflammation control and neuroprotection in experimental rabbit glaucoma model\",\"authors\":\"Okyanus Bulut Tarlabolen, Mine Esen Baris, Emrah Soylu, Banu Yaman, Timur Kose, Suzan Guvenyilmaz\",\"doi\":\"10.1111/aos.17102\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <section>\\n \\n <p><b>Aims/Purpose:</b> The aim of the study is to create a microbead induced ocular hypertension (OHT) model in rabbits, and to evaluate the effects of intravitreal and intraperitoneal injections of Adalimumab (ADA) on the number of retinal ganglion cells (RGC), retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness.</p>\\n \\n <p><b>Methods:</b> 15 rabbits of mixed strain (9–12 months old, 3.5-4kg) were randomized into 4 groups. OHT was induced with microbead injection into the anterior chamber of right eyes. On 7th, 14th days of OHT, ADA was injected at one of two concentrations (2.5mg group 1: G1/5mg group 2:G2) into right eyes of two groups, intraperitoneally 5mg/kg into the third group (G3), and balanced salt solution into fourth group (sham). The left eyes were used as controls. At 40<sup>th</sup> day, the rabbits were euthanized. Retinal and optic nerve head (ONH) histology was studied with hematoxylin-eosin and toluidine blue staining.</p>\\n \\n <p><b>Results:</b> OHT was induced with microbeads in 13 eyes. 2 rabbits were excluded (endophthalmitis, total hyphema). The average pre-OHT IOP from all eyes 9.7±09mmHg (8-11). Statistically significant IOP increase was observed in all subject eyes on day 7 (14±1.4 (12-18)) (<i>p</i> = 0.01) and maintained until ADA injection (day 21). RGCs in the eyes with elevated IOP were 7.2±1.2 and 7.6±1.5, 6.3+1.1 cells in ADA treated groups, G1, G2, G3, respectively. There was no statistically significant difference between treatment groups. The average RNFL was 125.9±10.9 μm in control, 60.2±9.4 μm in G1, 45.7±2.9 μm in G2, 22.8±2.9 μm in G3, 21.7±10 μm in sham. Significant elevation was observed in G1 compared to all treatment groups. (<i>p</i> = 0.01). The average GCC of control was 45.5±1.9 μm, G1 41.2±2.2 μm, G2 39.3±3.3 μm, G3 34.1±1.6 μm, sham was 38.3±1.1 μm. Significant increase was observed in G1 compared to G3. (<i>p</i> = 0.01).</p>\\n \\n <p><b>Conclusions:</b> OHT triggers inflammatory response in which TNF-α expression is increased around the ONH. Blocking TNF-α might prevent axonal degeneration and RGC loss by inhibiting this response. These findings may further contribute to the literature for a new treatment strategy for glaucoma using TNF-α antagonists or inflammation suppressors.</p>\\n </section>\\n </div>\",\"PeriodicalId\":6915,\"journal\":{\"name\":\"Acta Ophthalmologica\",\"volume\":\"103 S284\",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-01-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/10.1111/aos.17102\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Ophthalmologica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/aos.17102\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Ophthalmologica","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/aos.17102","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
Effectiveness of intravitreal antitNF-ALFA for neuroinflammation control and neuroprotection in experimental rabbit glaucoma model
Aims/Purpose: The aim of the study is to create a microbead induced ocular hypertension (OHT) model in rabbits, and to evaluate the effects of intravitreal and intraperitoneal injections of Adalimumab (ADA) on the number of retinal ganglion cells (RGC), retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness.
Methods: 15 rabbits of mixed strain (9–12 months old, 3.5-4kg) were randomized into 4 groups. OHT was induced with microbead injection into the anterior chamber of right eyes. On 7th, 14th days of OHT, ADA was injected at one of two concentrations (2.5mg group 1: G1/5mg group 2:G2) into right eyes of two groups, intraperitoneally 5mg/kg into the third group (G3), and balanced salt solution into fourth group (sham). The left eyes were used as controls. At 40th day, the rabbits were euthanized. Retinal and optic nerve head (ONH) histology was studied with hematoxylin-eosin and toluidine blue staining.
Results: OHT was induced with microbeads in 13 eyes. 2 rabbits were excluded (endophthalmitis, total hyphema). The average pre-OHT IOP from all eyes 9.7±09mmHg (8-11). Statistically significant IOP increase was observed in all subject eyes on day 7 (14±1.4 (12-18)) (p = 0.01) and maintained until ADA injection (day 21). RGCs in the eyes with elevated IOP were 7.2±1.2 and 7.6±1.5, 6.3+1.1 cells in ADA treated groups, G1, G2, G3, respectively. There was no statistically significant difference between treatment groups. The average RNFL was 125.9±10.9 μm in control, 60.2±9.4 μm in G1, 45.7±2.9 μm in G2, 22.8±2.9 μm in G3, 21.7±10 μm in sham. Significant elevation was observed in G1 compared to all treatment groups. (p = 0.01). The average GCC of control was 45.5±1.9 μm, G1 41.2±2.2 μm, G2 39.3±3.3 μm, G3 34.1±1.6 μm, sham was 38.3±1.1 μm. Significant increase was observed in G1 compared to G3. (p = 0.01).
Conclusions: OHT triggers inflammatory response in which TNF-α expression is increased around the ONH. Blocking TNF-α might prevent axonal degeneration and RGC loss by inhibiting this response. These findings may further contribute to the literature for a new treatment strategy for glaucoma using TNF-α antagonists or inflammation suppressors.
期刊介绍：
Acta Ophthalmologica is published on behalf of the Acta Ophthalmologica Scandinavica Foundation and is the official scientific publication of the following societies: The Danish Ophthalmological Society, The Finnish Ophthalmological Society, The Icelandic Ophthalmological Society, The Norwegian Ophthalmological Society and The Swedish Ophthalmological Society, and also the European Association for Vision and Eye Research (EVER).
Acta Ophthalmologica publishes clinical and experimental original articles, reviews, editorials, educational photo essays (Diagnosis and Therapy in Ophthalmology), case reports and case series, letters to the editor and doctoral theses.
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