School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK.
UK Dementia Research Institute, Hadyn Ellis Building, Cardiff University, Cardiff, UK.
Methods Mol Biol. 2025;2858:191-205. doi: 10.1007/978-1-0716-4140-8_16.
The detection of selective retinal ganglion cell damage in glaucoma has been a long sought-after goal, not just for the development of clinical tests for the early detection of glaucoma but for the elucidation of potential mechanisms underlying retinal ganglion cell loss. Early reports of the selective vulnerability of larger retinal ganglion cells (RGCs) in human studies did not translate simply to the loss of a particular class of RGC but more likely reflected shrinkage and degeneration across all RGC classes. Subsequent studies of nonhuman primate (NHP) models of glaucoma indicated some selectivity with great damage to the magnocellular vs parvocellular pathways. More recently, rodent models of experimental glaucoma have highlighted a selective vulnerability of OFF-centered RGCs-particularly those with transient responses. Selectivity for OFF pathway damage is also seen as a trend in a rat model of glaucoma. These data support the concept that some RGCs are more vulnerable to the effects of glaucoma damage. This chapter covers some of the methods to elucidate RGC damage and the relevance of model selection to mimic human glaucoma rather than just RGC death.
青光眼选择性视网膜神经节细胞损伤的检测一直是人们长期以来追求的目标，不仅是为了开发用于青光眼早期检测的临床测试，也是为了阐明视网膜神经节细胞丢失的潜在机制。早期在人类研究中关于较大的视网膜神经节细胞（RGC）选择性易损性的报告并不能简单地转化为特定 RGC 类别的损失，而更可能反映了所有 RGC 类别的收缩和退化。随后对青光眼非人类灵长类动物（NHP）模型的研究表明，在大细胞与小细胞通路中存在一定的选择性，大细胞损伤更为严重。最近，实验性青光眼的啮齿动物模型突出了 OFF 中心 RGC 的选择性易损性，尤其是具有瞬时反应的 RGC。在青光眼的大鼠模型中也观察到了对 OFF 通路损伤的选择性。这些数据支持了一些 RGC 对青光眼损伤更敏感的观点。本章介绍了一些阐明 RGC 损伤的方法，以及选择模型模拟人类青光眼而不仅仅是 RGC 死亡的相关性。
