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玻璃体内注射帕尼单抗与兔激光诱导性视网膜变性中视网膜色素上皮细胞增殖

Intravitreal panitumumab and retinal pigment epithelium proliferation in laser-induced retinal degeneration in rabbits.

作者信息

Bikbov Mukharram M, Kazakbaeva Gyulli M, Panda-Jonas Songhomitra, Valishin Iskander D, Nizamutdinova Aigul M, Jonas Jost B

机构信息

Ufa Eye Research Institute, Bashkir State Medical University, Ufa, Russia.

Department of Ophthalmology, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.

出版信息

Front Ophthalmol (Lausanne). 2025 Aug 7;5:1641194. doi: 10.3389/fopht.2025.1641194. eCollection 2025.

Abstract

PURPOSE

This study aims to examine the effect of intravitreally applied epidermal growth factor (EGF) receptor blocker panitumumab on the proliferation of retinal pigment epithelium cells (RPE) in an experimental model of localized retinal degeneration.

METHODS

The experimental study included rabbits with age of 2 to 3 months and body weight of 2.5-3 kg and which were randomly distributed into a study group and control group. The right eyes received two retinal argon laser coagulation spots (500 mW; diameter, 100 μm; duration, 0.5 s), applied with an interval of 2 min at the same location close to the vascular streak in the posterior fundus region. For five times at 2-day intervals, the rabbits of the study group received intravitreal injections of 1 mg panitumumab (0.10 mL), and the rabbits of the control group had intravitreal injections of 0.10 mL Ringer's solution. At baseline, at each time point of re-examination, and at study end, the animals were examined by fundus photography and optical coherence tomography of the laser spot.

RESULTS

The study included 19 rabbits (study group: 10 animals; control group: nine animals). After the third injection and at study end, the laser-induced area of depigmentation + hyperpigmentation combined did not vary significantly between the study group and the control group (1.43 ± 0.63 mm versus 1.63 ± 0.77 mm; = 0.56; and 1.37 ± 0.63 mm versus 1.61 ± 0.74 mm; = 0.46, respectively). At the same time points, the area with hyperpigmentation was significantly smaller in the study group than in the control group (0.16 ± 0.15 mm versus 0.80 ± 0.59 mm; = 0.01; and 0.14 ± 0.14 mm versus 0.70 ± 0.56 mm; = 0.02, respectively). At the same time points, the ratio of the hyperpigmented area to the combined depigmented + hyperpigmented area was significantly smaller in the study group than in the control group (0.11 ± 0.09 versus 0.43 ± 0.19 mm; < 0.001; and 0.10 ± 0.08 versus 0.35 ± 0.23mm; = 0.006, respectively).

CONCLUSIONS

These findings indicate that intravitreally administered panitumumab was associated with reduced subretinal hyperpigmentation in a laser-induced model of retinal injury. While this may reflect a modulation of the RPE response, including the potential suppression of RPE proliferation, further studies incorporating histological and molecular analyses are warranted to confirm its effect on subretinal fibrosis.

摘要

目的

本研究旨在探讨玻璃体内注射表皮生长因子(EGF)受体阻滞剂帕尼单抗对局部视网膜变性实验模型中视网膜色素上皮细胞(RPE)增殖的影响。

方法

实验研究纳入2至3个月龄、体重2.5 - 3千克的兔子,随机分为研究组和对照组。右眼在眼底后极部靠近血管弓的同一位置接受两个视网膜氩激光凝固斑(500毫瓦;直径100微米;持续时间0.5秒),间隔2分钟施加。研究组兔子每隔2天玻璃体内注射1毫克帕尼单抗(0.10毫升),共5次;对照组兔子玻璃体内注射0.10毫升林格氏液。在基线、每次复查时间点及研究结束时,通过眼底照相和激光斑的光学相干断层扫描对动物进行检查。

结果

本研究包括19只兔子(研究组:10只动物;对照组:9只动物)。第三次注射后及研究结束时,研究组和对照组激光诱导的色素脱失 + 色素沉着联合区域无显著差异(分别为1.43±0.63毫米对1.63±0.77毫米;P = 0.56;以及1.37±0.63毫米对1.61±0.74毫米;P = 0.46)。在相同时间点,研究组色素沉着区域明显小于对照组(分别为0.16±0.15毫米对0.80±0.59毫米;P = 0.01;以及0.14±0.14毫米对0.70±0.56毫米;P = 0.02)。在相同时间点,研究组色素沉着区域与色素脱失 + 色素沉着联合区域的比值明显小于对照组(分别为0.11±0.09对0.43±0.19毫米;P < 0.001;以及0.10±0.08对0.35±0.23毫米;P = 0.006)。

结论

这些发现表明,在激光诱导的视网膜损伤模型中,玻璃体内注射帕尼单抗与视网膜下色素沉着减少有关。虽然这可能反映了RPE反应的调节,包括对RPE增殖的潜在抑制,但需要进一步纳入组织学和分子分析的研究来证实其对视网膜下纤维化的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6c4/12367493/564dfb19e229/fopht-05-1641194-g001.jpg

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