中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (4): 795-796.doi: 10.4103/1673-5374.322457

• 观点:视神经损伤修复保护与再生 • 上一篇    下一篇

糖尿病视网膜病变:需要神经保护和再生疗法的神经血管疾病

  

  • 出版日期:2022-04-15 发布日期:2021-10-16

Diabetic retinopathy: neurovascular disease requiring neuroprotective and regenerative therapies

Toshiyuki Oshitari*   

  1. Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Inohana, Chuo-ku, Chiba; Department of Ophthalmology, International University of Health and Welfare School of Medicine, Kozunomori, Narita, Chiba, Japan
  • Online:2022-04-15 Published:2021-10-16
  • Contact: Toshiyuki Oshitari, MD, PhD, Tarii@aol.com.
  • Supported by:
    The present work is supported by a Grant-in-Aid from the Ministry of Education, Science, Sports, and Culture of Japanese Government.

摘要: Neural Regen Res:糖尿病视网膜病变与神经保护和再生疗法的相关性
    糖尿病视网膜病变是一种神经血管疾病,伴有由神经元、胶质细胞和血管细胞组成的神经血管单位功能障碍。许多研究证明神经元异常(如神经元细胞死亡)经常发展为血管异常,包括新生血管。神经细胞死亡和轴突变性是正常生理条件下不可逆的改变,与视力下降直接相关。在没有糖尿病视网膜病变的患者中,视网膜神经纤维层的厚度减少。神经节细胞复合体由视网膜神经纤维层、神经节细胞层和内网状层组成,其厚度减少0.54 mm/年,这与晚期青光眼中观察到的减少相似。这些临床结果表明轴突变性与糖尿病视网膜神经元异常的发病机制有关。因此,不仅需要神经保护,而且还需要再生疗法来保护和维持糖尿病视网膜病变眼睛的视觉功能。目前还不能保证同样有效治疗急性损伤的策略对慢性视网膜疾病有效。由于慢性视网膜疾病的细胞死亡途径可能比急性损伤更为复杂,同样的神经保护剂可能无法完全挽救神经元细胞死亡。再生药物必须长期应用。临床试验中已使用局部应用神经保护和再生剂。血液供应方法是一种选择,但是从长远来看,必须考虑副作用。这就是为什么研究人员选择了局部灌注方法来治疗糖尿病视网膜病变的神经保护疗法。
    来自日本千叶大学医学研究生院的Toshiyuki Oshitari计划在不久的将来对糖尿病动物模型进行局部联合治疗。简单地说,Diabetic Torrii大鼠将被用于研究,局部灌注药物为100mm TUDCA、100mm胞苷、10ng/mL NT-4、TUDCA和NT-4联合用药,以及TUDCA、胞苷和NT-4及PBS的联合用药。这些药物将每天两次,持续3个月。三个月后,将通过视网膜神经节细胞计数、GAP-43免疫染色、光学相干层析和视网膜电图检查这些药物的疗效。为了全面预防糖尿病视网膜病变的进展,临床医师不应忽视糖尿病视网膜病变血管异常进展后神经异常的进展。由于轴突变性与糖尿病视网膜病变患者视力丧失有一定的相关性,因此,不仅需要神经保护,而且还需要轴突保护和再生来保护视觉功能。糖尿病视网膜病变的病理机制并不简单,这意味着神经保护和再生治疗不容易建立。在进行临床试验之前,必须重新考虑糖尿病视网膜病变的神经保护和再生的治疗策略。否则,我们可能会损失很多时间和精力,以及糖尿病视网膜病变患者。
    文章在《中国神经再生研究(英文版)》杂志2022年 4 月  4 期发表。


https://orcid.org/0000-0002-8273-845X (Toshiyuki Oshitari) 

Abstract: It is well known that diabetic retinopathy is a neurovascular disease that is accompanied by dysfunction of neurovascular units composed of neurons, glial cells, and vascular cells (Antonetti et al., 2012; Figure 1). Many studies have reported that the neuronal abnormalities, such as neuronal cell death, frequently precedes vascular abnormalities including neovascularization (Sohn et al., 2016). Neuronal cell death and axonal degeneration are irreversible changes under normal physiological conditions, and they are directly linked to the vision decrease. In fact, there is a reduction of the thickness of retinal nerve fiber layer in patients without diabetic retinopathy (Sohn et al., 2016). The reduction in the thickness of the ganglion cell complex, which is made up of the retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer, is 0.54 μm/year which is similar to the reduction observed in advanced glaucoma (Sohn et al., 2016). These clinical findings strongly indicated that the axonal degeneration is associated with the pathogenesis of neuronal abnormalities in diabetic retinas. Thus, not only neuroprotection but also regenerative therapies are required for the protection and maintenance of visual function of eyes with diabetic retinopathy.