Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, USA.
Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
Sci Rep. 2020 Mar 4;10(1):3972. doi: 10.1038/s41598-020-60931-5.
Deletion of dystrobrevin binding protein 1 has been linked to Hermansky-Pudlak syndrome type 7 (HPS-7), a rare disease characterized by oculocutaneous albinism and retinal dysfunction. We studied dysbindin-1 null mutant mice (Dys) to shed light on retinal neurodevelopment defects in HPS-7. We analyzed the expression of a focused set of miRNAs in retina of wild type (WT), Dys and Dys mice. We also investigated the retinal function of these mice through electroretinography (ERG). We found that miR-101-3p, miR-137, miR-186-5p, miR-326, miR-382-5p and miR-876-5p were up-regulated in Dysmice retina. Dys mice showed significant increased b-wave in ERG, compared to WT mice. Bioinformatic analysis highlighted that dysregulated miRNAs target synaptic plasticity and dopaminergic signaling pathways, affecting retinal functions of Dys mice. Overall, the data indicate potential mechanisms in retinal neurodevelopment of Dys mice, which may have translational significance in HSP-7 patients, both in terms of diagnostic/prognostic biomarkers and novel pharmacological targets.
缺失 dystrobrevin 结合蛋白 1 与 Hermansky-Pudlak 综合征 7 型（HPS-7）有关，这是一种罕见的疾病，其特征是眼皮肤白化病和视网膜功能障碍。我们研究了 dysbindin-1 缺失突变小鼠（Dys），以阐明 HPS-7 中的视网膜神经发育缺陷。我们分析了野生型（WT）、Dys 和 Dys 小鼠视网膜中一组特定 miRNA 的表达。我们还通过视网膜电图（ERG）研究了这些小鼠的视网膜功能。我们发现 miR-101-3p、miR-137、miR-186-5p、miR-326、miR-382-5p 和 miR-876-5p 在 Dys 小鼠的视网膜中上调。与 WT 小鼠相比，Dys 小鼠的 ERG 中 b 波显著增加。生物信息学分析突出表明，失调的 miRNA 靶向突触可塑性和多巴胺能信号通路，影响 Dys 小鼠的视网膜功能。总的来说，这些数据表明 Dys 小鼠视网膜神经发育的潜在机制，这可能对 HSP-7 患者具有转化意义，无论是在诊断/预后生物标志物还是新型药物靶点方面。
