Conditioned media from dental pulp stem cells to counteract the age-related macular degeneration

IF 3 3区医学 Q1 OPHTHALMOLOGY Acta Ophthalmologica Pub Date : 2025-01-19 DOI:10.1111/aos.16936

Darin Zerti, Giulia Carozza, Fanny Pulcini, Loreto Lancia, Vincenzo Mattei, Simona Delle Monache, Rita Maccarone

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Abstract

Aims/Purpose: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. To date, there are no effective therapies to counteract the AMD towards the most severe stages characterized by a progressive loss of photoreceptors triggered by retinal pigmented epithelium dysfunction. Given their easily source and their high proliferative potential, Dental Pulp Stem Cells (DPSCs) showed promise for regenerative medicine. The main advantage of DPSCs is related to their immunosuppressive and immunoregulatory abilities, including the capability to promote regeneration of damaged tissues. It is well known the therapeutic potential of DPSCs secretome (conditioned media, CM), including trophic factors and cytokines, as a treatment of neurogenerative diseases. We evaluated the capability of DPSCs-CM cultured in hypoxia and normoxic conditions to counteract retinal degeneration in an animal model of AMD.

Methods: DPSCs-CM were intravitreally injected the day before the exposure of albino rats to high intensity light (LD). We evaluated the retinal function, and we performed morphological and molecular analysis a week after the LD, in accordance with the well-established protocol of our light damage model.

Results: DPSCs-CM obtained from hypoxia or normoxia, were able to preserve the retinal function, to reduce microglial activation and their migration toward outer nuclear layer (ONL). Furthermore, we demonstrated that the treatment with normoxic DPSCs-CM limited the hot spot extension and preserved the ONL thickness better than the hypoxic DPSCs-CM. The different concentrations of growth factors and cytokines detected in both CM played a key role in the understanding of the greatest protective effect of the normoxic-CM compared to hypoxic-CM.

Conclusions: Taken together, our study demonstrated that normoxic DPSCs-CM represents an eligible candidate to counteract retinal degeneration and, therefore, a promising therapeutic agent for AMD.

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目的/宗旨：老年性黄斑变性（AMD）是导致老年人失明的主要原因。视网膜色素上皮细胞功能障碍导致光感受器逐渐丧失，到目前为止，还没有有效的疗法来应对最严重阶段的老年黄斑变性。牙髓干细胞（DPSC）来源容易，增殖潜力大，因此有望用于再生医学。牙髓干细胞的主要优势在于其免疫抑制和免疫调节能力，包括促进受损组织再生的能力。众所周知，包括营养因子和细胞因子在内的 DPSCs 分泌物（条件培养基，CM）具有治疗神经退行性疾病的潜力。我们评估了在低氧和常氧条件下培养的 DPSCs-CM 对抗 AMD 动物模型视网膜退化的能力。方法：在白化大鼠暴露于高强度光（LD）的前一天，经静脉注射 DPSCs-CM。我们评估了视网膜功能，并按照光损伤模型的既定方案，在照射一周后进行了形态学和分子分析。结果从缺氧或常氧环境中获得的 DPSCs-CM 能够保护视网膜功能，减少小胶质细胞的活化及其向核外层（ONL）的迁移。此外，我们还发现，与低氧DPSCs-CM相比，常氧DPSCs-CM能更好地限制热点的扩展并保持ONL的厚度。在两种CM中检测到的生长因子和细胞因子浓度不同，这对理解常氧CM比缺氧CM的最大保护效果起到了关键作用。结论：综上所述，我们的研究表明，常氧 DPSCs-CM 是对抗视网膜变性的合格候选物质，因此是一种治疗老年性视网膜病变的有前途的药物。

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来源期刊

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.