Ruzafa Noelia, Pereiro Xandra, Fonollosa Alex, Araiz Javier, Acera Arantxa, Vecino Elena
Experimental Ophthalmo-Biology Group, Department of Cell Biology and Histology, University of Basque Country UPV/EHU, Leioa, Spain.
Begiker-Ophthalmology Research Group, Cruces Hospital, BioCruces Health Research Institute, Bilbao, Spain.
Front Pharmacol. 2021 Mar 9;12:606275. doi: 10.3389/fphar.2021.606275. eCollection 2021.
Plasma rich in growth factors (PRGF) is a subtype of platelet-rich plasma (PRP) that stimulates tissue regeneration and may promote neuronal survival. It has been employed in ophthalmology to achieve tissue repair in some retinal pathologies, although how PRGF acts in the retina is still poorly understood. As a part of the central nervous system, the retina has limited capacity for repair capacity following damage, and retinal insult can provoke the death of retinal ganglion cells (RGCs), potentially producing irreversible blindness. RGCs are in close contact with glial cells, such as Müller cells, that help maintain homeostasis in the retina. In this study, the aim was to determine whether PRGF can protect RGCs and whether it increases the number of Müller cells. Therefore, PRGF were tested on primary cell cultures of porcine RGCs and Müller cells, as well as on co-cultures of these two cell types. Moreover, the inflammatory component of PRGF was analyzed and the cytokines in the different PRGFs were quantified. In addition, we set out to determine if blocking the inflammatory components of PRGF alters its effect on the cells in culture. The presence of PRGF compromises RGC survival in pure cultures and in co-culture with Müller cells, but this effect was reversed by heat-inactivation of the PRGF. The detrimental effect of PRGF on RGCs could be in part due to the presence of cytokines and specifically, to the presence of pro-inflammatory cytokines that compromise their survival. However, other factors are likely to be present in the PRGF that have a deleterious effect on the RGCs since the exposure to antibodies against these cytokines were insufficient to protect RGCs. Moreover, PRGF promotes Müller cell survival. In conclusion, PRGF hinders the survival of RGCs in the presence or absence of Müller cells, yet it promotes Müller cell survival that could be the reason of retina healing observed in the treatments, with some cytokines possibly implicated. Although PRGF could stimulate tissue regeneration, further studies should be performed to evaluate the effect of PRGF on neurons and the implication of its potential inflammatory role in such processes.
富含生长因子的血浆（PRGF）是富血小板血浆（PRP）的一种亚型，可刺激组织再生并可能促进神经元存活。它已被应用于眼科领域，以实现某些视网膜病变的组织修复，尽管PRGF在视网膜中的作用机制仍知之甚少。作为中枢神经系统的一部分，视网膜受损后的修复能力有限，视网膜损伤可引发视网膜神经节细胞（RGCs）死亡，进而可能导致不可逆的失明。RGCs与神经胶质细胞（如Müller细胞）紧密接触，这些神经胶质细胞有助于维持视网膜的内环境稳定。在本研究中，目的是确定PRGF是否能保护RGCs以及它是否会增加Müller细胞的数量。因此，对猪RGCs和Müller细胞的原代细胞培养物以及这两种细胞类型的共培养物进行了PRGF测试。此外，分析了PRGF的炎症成分并对不同PRGF中的细胞因子进行了定量。另外，我们着手确定阻断PRGF的炎症成分是否会改变其对培养细胞的影响。PRGF的存在会损害纯培养物以及与Müller细胞共培养时RGCs的存活，但这种作用可通过PRGF的热灭活而逆转。PRGF对RGCs的有害作用可能部分归因于细胞因子的存在，特别是促炎细胞因子的存在会损害它们的存活。然而，PRGF中可能还存在其他对RGCs有有害影响的因素，因为暴露于针对这些细胞因子的抗体不足以保护RGCs。此外，PRGF可促进Müller细胞存活。总之，无论有无Müller细胞存在，PRGF都会阻碍RGCs的存活，但它能促进Müller细胞存活，这可能是治疗中观察到视网膜愈合的原因，其中一些细胞因子可能与此有关。尽管PRGF可以刺激组织再生，但仍需进一步研究以评估PRGF对神经元的影响及其潜在炎症作用在此类过程中的意义。
