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手术去除 RPE 导致的外视网膜萎缩的兔模型。

A rabbit model for outer retinal atrophy caused by surgical RPE removal.

机构信息

Eye Clinic Sulzbach, Knappschaft Hospital Saar, Sulzbach/Saar, Germany.

Fraunhofer Institute for Biomedical Engineering, Sulzbach/Saar, Germany.

出版信息

Graefes Arch Clin Exp Ophthalmol. 2023 Aug;261(8):2265-2280. doi: 10.1007/s00417-023-06014-3. Epub 2023 Mar 28.

Abstract

PURPOSE

We aimed to establish a rabbit model with retinal atrophy induced by an iatrogenic retinal pigment epithelium (RPE) removal, for future testing of the efficacy and safety of cell therapy strategies.

METHODS

A localized detachment of the retina from the RPE/choroid layer was created in 18 pigmented rabbits. The RPE was removed by scraping with a custom-made extendable loop instrument. The resulting RPE wound was observed over a time course of 12 weeks with optical coherence tomography and angiography. After 4 days (group 1) and 12 weeks (group 2), histology was done and staining with hematoxylin and eosin, as well as immunofluorescence performed to further investigate the effects of debridement on the RPE and the overlying retina.

RESULTS

Already after 4 days, we observed a closure of the RPE wound by proliferating RPE and microglia/macrophage cells forming a multilayered clump. This pattern continued over the observation time course of 12 weeks, whereby the inner and outer nuclear layer of the retina became atrophic. No neovascularization was observed in the angiograms or histology. The observed changes were limited to the site of the former RPE wound.

CONCLUSIONS

Localized surgical RPE removal induced an adjacent progressive retinal atrophy. Altering the natural course of this model may serve as a basis to test RPE cell therapeutics.

摘要

目的

我们旨在建立一种由医源性视网膜色素上皮(RPE)去除引起的视网膜萎缩的兔模型,以便未来测试细胞治疗策略的疗效和安全性。

方法

在 18 只色素兔中,通过定制的可扩展环器械刮除来局部分离视网膜与 RPE/脉络膜层。通过光学相干断层扫描和血管造影术在 12 周的时间过程中观察 RPE 伤口。在 4 天(第 1 组)和 12 周(第 2 组)后进行组织学检查,并进行苏木精和伊红染色以及免疫荧光染色,以进一步研究清创对 RPE 和其上覆的视网膜的影响。

结果

在第 4 天,我们已经观察到增殖的 RPE 和微胶质细胞/巨噬细胞形成多层团块来封闭 RPE 伤口。这种模式在 12 周的观察过程中持续存在,导致视网膜的内核层和外核层萎缩。血管造影或组织学检查均未观察到新生血管。观察到的变化仅限于原 RPE 伤口部位。

结论

局部手术 RPE 去除会导致相邻的进行性视网膜萎缩。改变这种模型的自然病程可能为测试 RPE 细胞治疗提供基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d35/10368565/3267489f7908/417_2023_6014_Fig1_HTML.jpg

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