Effectiveness of intravitreal antitNF-ALFA for neuroinflammation control and neuroprotection in experimental rabbit glaucoma model

IF 3 3区医学 Q1 OPHTHALMOLOGY Acta Ophthalmologica Pub Date : 2025-01-19 DOI:10.1111/aos.17102

Okyanus Bulut Tarlabolen, Mine Esen Baris, Emrah Soylu, Banu Yaman, Timur Kose, Suzan Guvenyilmaz

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Abstract

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 40^th 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.

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目的：本研究旨在建立微珠诱导的兔子眼压升高（OHT）模型，并评估阿达木单抗（ADA）玻璃体内注射和腹腔注射对视网膜神经节细胞（RGC）数量、视网膜神经纤维层（RNFL）和神经节细胞复合体（GCC）厚度的影响。方法：将 15 只混合品系的兔子（9-12 个月大，3.5-4 千克）随机分为 4 组。右眼前房注射微珠诱导 OHT。在 OHT 第 7 天和第 14 天，向两组的右眼注射两种浓度之一的 ADA（2.5 毫克组 1：G1/5 毫克组 2：G2），向第三组（G3）腹腔注射 5 毫克/千克，向第四组（假）注射平衡盐溶液。左眼作为对照组。第 40 天，兔子被安乐死。用苏木精-伊红和甲苯胺蓝染色法研究视网膜和视神经头组织学。结果用微珠诱导了 13 只兔子的 OHT。2只兔子被排除在外（眼底病、全眼球下垂）。所有眼睛 OHT 前的平均眼压为 9.7±09mmHg (8-11)。在第 7 天（14±1.4 (12-18)）（p = 0.01），所有受试者的眼压都出现了统计学意义上的明显升高，并一直维持到注射 ADA（第 21 天）。眼压升高组 G1、G2 和 G3 的 RGCs 分别为 7.2±1.2 和 7.6±1.5，6.3+1.1 个细胞。治疗组之间的差异无统计学意义。对照组的平均 RNFL 为 125.9±10.9μm，G1 为 60.2±9.4μm，G2 为 45.7±2.9μm，G3 为 22.8±2.9μm，假性组为 21.7±10μm。与所有治疗组相比，G1 观察到显著升高。(p = 0.01).对照组的平均 GCC 为 45.5±1.9μm，G1 为 41.2±2.2μm，G2 为 39.3±3.3μm，G3 为 34.1±1.6μm，假体为 38.3±1.1μm。与 G3 相比，G1 观察到显著增加。(p = 0.01). 结论OHT 会引发炎症反应，使 ONH 周围的 TNF-α 表达增加。阻断 TNF-α 可抑制这种反应，从而防止轴突变性和 RGC 损失。这些发现可能会进一步促进文献研究，为使用TNF-α拮抗剂或炎症抑制剂治疗青光眼提供新的治疗策略。

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来源期刊

Acta Ophthalmologica 医学-眼科学

CiteScore

7.60

自引率

5.90%

发文量

433

审稿时长

6 months

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.