Glaucoma and Retinal Neurodegeneration Group, UCL Institute of Ophthalmology, London, UK.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Expert Opin Investig Drugs. 2021 May;30(5):571-577. doi: 10.1080/13543784.2021.1896701. Epub 2021 Apr 1.
Retinal neurodegeneration causes irreversible vision loss, impairing quality of life. By targeting neurotoxic conditions, such as oxidative stress and ischemia, neuroprotectants can slow or stop sight loss resulting from eye disease. Despite limimted clinical use of neuroprotectants, there are several promising compounds in early clinical trials (pre-phase III) which may fulfil new therapeutic roles. Search terms relating to neuroprotection and eye disease were used on ClinicalTrials.gov to identify neuroprotective candidates.
Research supporting neuroprotection in eye diseases is focused on, ranging from preclinical to phase II, according to the ClinicalTrials.gov database. The compounds discussed are explored in terms of future clinical applications.
The major challenge in neuroprotection research is translation from basic research to the clinic. A number of potential neuroprotectants have progressed to ophthalmology clinical trials in recent years, with defined mechanisms of action - saffron and CoQ10 - targeting mitochondria, and both CNTF and NGF showing anti-apoptotic effects. Enhancements in trial design and patient cohorts in proof-of-concept trials with enriched patient populations and surrogate endpoints should accelerate drug development. A further important consideration is optimising drug delivery to improve individualised management and patient compliance. Progress in these areas means that neuroprotective strategies have a much improved chance of translational success.
视网膜神经退行性病变导致不可逆转的视力丧失，降低生活质量。通过针对氧化应激和缺血等神经毒性情况，神经保护剂可以减缓或阻止眼部疾病导致的视力丧失。尽管神经保护剂的临床应用有限，但仍有几种有前途的化合物处于早期临床试验（三期前）阶段，这些化合物可能具有新的治疗作用。使用临床试验数据库中的“神经保护和眼病”相关检索词来确定神经保护候选药物。
根据临床试验数据库，研究重点是从临床前到二期的眼部疾病神经保护作用。讨论的化合物是根据未来的临床应用来探讨的。
神经保护研究的主要挑战是将基础研究转化为临床实践。近年来，一些潜在的神经保护剂已经进入眼科临床试验，具有明确的作用机制-藏红花和 CoQ10 靶向线粒体，而 CNTF 和 NGF 均显示出抗细胞凋亡作用。在具有丰富患者群体和替代终点的概念验证试验中，通过改进试验设计和患者群体，可以加速药物开发。另一个重要考虑因素是优化药物输送，以提高个体化管理和患者依从性。在这些领域的进展意味着神经保护策略有更好的转化成功机会。
