Department of Molecular Biomedicine, Centro de Investigaciones Biológicas Margarita Salas (CSIC), Madrid, Spain.
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain.
Adv Exp Med Biol. 2023;1415:409-413. doi: 10.1007/978-3-031-27681-1_60.
Retinitis pigmentosa (RP) is a genetically heterogeneous disease and the predominant cause of hereditary blindness. Irrespective of the causative mutation, traits common to all forms of RP include photoreceptor dysfunction and death, activation of the retinal glial component, and retinal inflammation. Activation of Toll-like receptors (TLRs) in response to tissue damage is associated with inflammatory processes that contribute to neurodegeneration. We show that retinal expression of the genes Tlr1 to Tlr9 is increased in the rd10 mouse model of RP, with Tlr2 showing the greatest increase (36-fold). Flow cytometry analysis of the retinal myeloid population revealed significant increases in numbers of microglia and infiltrating monocytes and macrophages in rd10 retinas. Furthermore, TLR2 expression, which was restricted to myeloid cells, was increased in rd10 retinal microglia. These observations, together with our previous finding of delayed RP progression following Tlr2 deletion, point to TLR2 as a potential therapeutic target for RP.
色素性视网膜炎（RP）是一种遗传异质性疾病，也是遗传性失明的主要原因。无论致病突变如何，所有形式的 RP 都具有共同的特征，包括感光器功能障碍和死亡、视网膜神经胶质成分的激活以及视网膜炎症。Toll 样受体（TLR）对组织损伤的激活与导致神经退行性变的炎症过程有关。我们发现，在 RP 的 rd10 小鼠模型中，视网膜中 Tlr1 到 Tlr9 的基因表达增加，其中 Tlr2 的增加最为显著（36 倍）。对视网膜髓样细胞群体的流式细胞术分析显示，rd10 视网膜中的小胶质细胞和浸润的单核细胞和巨噬细胞数量显著增加。此外，TLR2 的表达仅限于髓样细胞，在 rd10 视网膜小胶质细胞中也增加了。这些观察结果，以及我们之前发现 TLR2 缺失后 RP 进展延迟的结果，表明 TLR2 可能是 RP 的一个潜在治疗靶点。
