Rosa João Gabriel Santos, Bernardo Jefferson Thiago Gonçalves, Álvarez Yolanda, Kennedy Breandán, Lima Carla, Lopes-Ferreira Monica
Immunoregulation Unit of the Laboratory of Applied Toxinology (CeTICs/FAPESP), Butantan Institute, São Paulo 05503-900, Brazil.
UCD Conway Institute of Biomolecular and Biomedical Research and UCD School of Biomolecular and Biomedical Science, University College Dublin, D04 V1W8 Dublin, Ireland.
Pharmaceuticals (Basel). 2025 Jun 4;18(6):840. doi: 10.3390/ph18060840.
: The retina plays a vital role in vision, and its impairment can cause significant visual deficits. Current retinal disease treatments range from conventional anti-inflammatory drugs to advanced anti-VEGF therapies and monoclonal antibodies. TnP, a novel synthetic peptide in preclinical development, has demonstrated therapeutic potential in chronic inflammatory conditions such as multiple sclerosis and asthma due to its immunomodulatory properties. Using zebrafish-which share significant genetic homology with humans-we investigated TnP's effects on retinopathy models mimicking diabetic retinopathy (DR) through either cobalt chloride (CoCl)-induced hypoxia or light-induced retinal damage (LIRD). : We employed two retinal injury models (CoCl-induced hypoxia and LIRD) and subjected them to TnP treatment, assessing the outcomes through visual-motor response testing and histological examination. : CoCl exposure impaired swimming activity, while light damage reduced the movement distance. Both models induced distinct retinal morphological changes. Although TnP failed to reverse most injury effects, it specifically restored the inner plexiform layer (IPL)'s thickness. : Our findings suggest that TnP may enhance neuronal plasticity by promoting cell proliferation and synaptic connectivity. While showing promise as a therapeutic candidate for retinal and neurodegenerative disorders, TnP might achieve optimal efficacy when combined with complementary treatments.
视网膜在视觉中起着至关重要的作用,其损伤会导致严重的视力缺陷。目前视网膜疾病的治疗方法从传统的抗炎药物到先进的抗血管内皮生长因子(VEGF)疗法和单克隆抗体不等。TnP是一种处于临床前开发阶段的新型合成肽,由于其免疫调节特性,已在诸如多发性硬化症和哮喘等慢性炎症性疾病中显示出治疗潜力。利用与人类具有显著基因同源性的斑马鱼,我们研究了TnP对模拟糖尿病性视网膜病变(DR)的视网膜病变模型的影响,这些模型是通过氯化钴(CoCl)诱导的缺氧或光诱导的视网膜损伤(LIRD)建立的。我们采用了两种视网膜损伤模型(CoCl诱导的缺氧和LIRD),并对它们进行TnP治疗,通过视觉运动反应测试和组织学检查评估结果。CoCl暴露会损害游泳活动,而光损伤会减少移动距离。两种模型都诱导了明显的视网膜形态变化。尽管TnP未能逆转大多数损伤效应,但它特异性地恢复了内网状层(IPL)的厚度。我们的研究结果表明,TnP可能通过促进细胞增殖和突触连接来增强神经元可塑性。虽然TnP作为视网膜和神经退行性疾病的治疗候选药物显示出前景,但与补充治疗联合使用时,TnP可能会达到最佳疗效。