Neuroprotection of retinal ganglion cells by agonism of the beta but not the alpha oestrogen receptor in the axotomized retina of male and female mice.

IF 3 3区 医学 Q1 OPHTHALMOLOGY
Kristy T Rodríguez-Ramírez, Caridad Galindo-Romero, Fernando Lucas-Ruiz, Manuel Vidal-Sanz, Marta Agudo-Barriuso
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引用次数: 0

Abstract

Purpose: To compare the course of retinal ganglion cell (RGC) loss following optic nerve crush (ONC) in male and female mice and to assess the neuroprotective potential of intravitreally administered oestrogen receptor alpha (ERα) or beta (ERβ) agonists.

Methods: Optic nerve crush was performed on the left optic nerve of male and female C57BL/6 mice. RGC loss was evaluated at 3-21 days post-lesion. ERα and ERβ agonists (PPT and DPN, respectively) were injected either immediately after ONC with retinas analysed at 5 days or immediately post-ONC and again at 9 days, with retinas analysed at 21 days post-lesion. Intact retinas served as controls. The total population of Brn3a+RGCs was quantified in retinal flat mounts. To assess the retinal expression of ERα and ERβ, immunodetection was performed on cross sections, and the percentage of RGCs expressing each receptor was determined in flat mounts.

Results: Retinal ganglion cell loss in both sexes followed two distinct linear phases: A rapid phase up to 9 days post-lesion, followed by a slower phase. However, the onset of RGC loss was earlier in males than in females. Both ERα and ERβ were expressed in all retinal layers and by the majority of RGCs. While ERα agonism did not confer RGC protection, ERβ agonism was neuroprotective during the second phase of axotomy-induced RGC loss.

Conclusions: Preclinical results may be influenced by pooling data from male and female mice. The neuroprotective effects of ERβ during the second phase of RGC loss, likely linked to neuroinflammation, suggest potential therapeutic applications for chronic conditions such as glaucoma.

雌性雌激素受体而非雌性雌激素受体激动作用对雌雄小鼠视网膜神经节细胞的神经保护作用。
目的:比较雄性和雌性小鼠视神经压迫(ONC)后视网膜神经节细胞(RGC)损失的过程,并评估玻璃体内给药雌激素受体α (ERα)或β (ERβ)激动剂的神经保护作用。方法:对C57BL/6雌雄小鼠左视神经进行视神经挤压。在病变后3-21天评估RGC损失。在ONC后立即注射ERα和ERβ激动剂(分别为PPT和DPN),并在病变后5天分析视网膜,或在ONC后立即注射ERα和ERβ激动剂,并在病变后21天分析视网膜。完整的视网膜作为对照。Brn3a+RGCs的总数在视网膜扁平支架中被量化。为了评估ERα和ERβ的视网膜表达,在横切上进行免疫检测,并在平载中测定表达每种受体的RGCs的百分比。结果:两性视网膜神经节细胞的损失遵循两个不同的线性阶段:病变后9天的快速阶段,随后是较慢的阶段。然而,男性的RGC丧失发病时间比女性早。ERα和ERβ在所有视网膜层和大多数RGCs中均有表达。虽然ERα激动剂不具有RGC保护作用,但ERβ激动剂在肛门切开术诱导的RGC丢失的第二阶段具有神经保护作用。结论:汇集雄性和雌性小鼠的数据可能会影响临床前结果。在RGC缺失的第二阶段,ERβ的神经保护作用可能与神经炎症有关,这提示了青光眼等慢性疾病的潜在治疗应用。
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来源期刊
Acta Ophthalmologica
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.
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