Fernández-Sánchez Laura, Albertos-Arranz Henar, Ortuño-Lizarán Isabel, Lax Pedro, Cuenca Nicolás
Department of Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain.
Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
Front Neuroanat. 2022 Apr 12;16:858073. doi: 10.3389/fnana.2022.858073. eCollection 2022.
Retinitis pigmentosa is primarily characterized by a massive photoreceptor loss. But a global retinal remodeling occurs in later stages of the disease. At that phase, glial cells and retinal vasculature are also strongly affected. The main aim of the present work is to assess if the bile acid Tauroursodeoxicholic acid (TUDCA), which has a demonstrated neuroprotective effect in numerous neurodegenerative diseases, is able to prevent glial and vascular degeneration in the P23H rat retina.
Homozygous P23H (line 3) animals were injected weekly with a TUDCA (500 mg/kg, i.p.) or vehicle solution, from the postnatal day (P) 21 to P120. Sprague-Dawley rats (SD) were used as control. Retinal cross-sections and wholemounts were immunostained using different glial and vascular markers and visualized with confocal microscopy. Retinal blood vessels were stained with nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry and retinal vascular networks were drawn by hand using a camera lucida.
At P120, the photoreceptor degeneration observed in P23H rats was accompanied by a reduction in the vascular network density and complexity at the deep capillary plexus. In addition, astrocytes showed gliotic features and the outer processes of Müller cells displayed an aberrant distribution in ring-shaped structures. When treated with TUDCA, P23H rats displayed better-preserved vessels and capillary loops in the deep capillary plexus which are associated with the partial preservation of photoreceptors. TUDCA treatment also increased the number of astrocytes and reduced the presence of Müller cell process clusters in the outer retina.
This work suggests that, besides its neuroprotective effect on photoreceptor cells, TUDCA treatment also protects from vascular and glial degeneration, a fact that encourages the use of TUDCA as a powerful therapy for neurodegenerative diseases.
视网膜色素变性主要特征为大量光感受器丧失。但在疾病后期会发生全视网膜重塑。在此阶段，神经胶质细胞和视网膜血管也会受到严重影响。本研究的主要目的是评估在多种神经退行性疾病中已证明具有神经保护作用的胆汁酸牛磺熊去氧胆酸（TUDCA）是否能够预防P23H大鼠视网膜中的神经胶质和血管变性。
从出生后第21天（P）至P120，每周给纯合P23H（3号线）动物腹腔注射TUDCA（500 mg/kg）或溶剂溶液。使用Sprague-Dawley大鼠（SD）作为对照。视网膜切片和整装片用不同的神经胶质和血管标记物进行免疫染色，并用共聚焦显微镜观察。视网膜血管用烟酰胺腺嘌呤二核苷酸磷酸（NADPH）黄递酶组织化学染色，视网膜血管网络用明视野显微镜手工绘制。
在P120时，P23H大鼠中观察到的光感受器变性伴随着深层毛细血管丛处血管网络密度和复杂性的降低。此外，星形胶质细胞表现出胶质增生特征， Müller细胞的外突在环形结构中呈现异常分布。用TUDCA治疗时，P23H大鼠深层毛细血管丛中的血管和毛细血管环保存得更好，这与光感受器的部分保存有关。TUDCA治疗还增加了星形胶质细胞的数量，并减少了外视网膜中Müller细胞突起簇的存在。
这项研究表明，除了对光感受器细胞的神经保护作用外，TUDCA治疗还能防止血管和神经胶质变性，这一事实鼓励将TUDCA用作神经退行性疾病的有效治疗方法。
