Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA,
Mol Neurobiol. 2013 Dec;48(3):819-28. doi: 10.1007/s12035-013-8470-2. Epub 2013 May 25.
Crystallins are heterogeneous proteins classified into alpha, beta, and gamma families. Although crystallins were first identified as the major structural components of the ocular lens with a principal function to maintain lens transparency, further studies have demonstrated the expression of these proteins in a wide variety of tissues and cell types. Alpha crystallins (alpha A and alpha B) share significant homology with small heat shock proteins and have chaperone-like properties, including the ability to bind and prevent the precipitation of denatured proteins and to increase cellular resistance to stress-induced apoptosis. Stress-induced upregulation of crystallin expression is a commonly observed phenomenon and viewed as a cellular response mechanism against environmental and metabolic insults. However, several studies reported downregulation of crystallin gene expression in various models of glaucomatous nerodegeneration suggesting that that the decreased levels of crystallins may affect the survival properties of retinal ganglion cells (RGCs) and thus, be associated with their degeneration. This hypothesis was corroborated by increased survival of axotomized RGCs in retinas overexpressing alpha A or alpha B crystallins. In addition to RGC protective functions of alpha crystallins, beta and gamma crystallins were implicated in RGC axonal regeneration. These findings demonstrate the importance of crystallin genes in RGC survival and regeneration and further in-depth studies are necessary to better understand the mechanisms underlying the functions of these proteins in healthy RGCs as well as during glaucomatous neurodegeneration, which in turn could help in designing new therapeutic strategies to preserve or regenerate these cells.
晶状蛋白是具有异质性的蛋白质，可分为α、β和γ家族。虽然晶状蛋白最初被鉴定为眼睛晶状体的主要结构成分，主要功能是保持晶状体透明，但进一步的研究表明这些蛋白质在广泛的组织和细胞类型中表达。α 晶状蛋白（αA 和 αB）与小分子热休克蛋白具有显著同源性，具有伴侣样特性，包括结合和防止变性蛋白沉淀以及增加细胞对应激诱导细胞凋亡的抵抗力的能力。应激诱导的晶状蛋白表达上调是一种常见的现象，被视为细胞对环境和代谢损伤的反应机制。然而，几项研究报告了在各种青光眼神经变性模型中晶状蛋白基因表达的下调，表明晶状蛋白水平的降低可能影响视网膜神经节细胞（RGC）的存活特性，因此与它们的变性有关。这个假设在过表达αA 或 αB 晶状蛋白的视网膜中被证实，即轴突切断的 RGC 存活率增加。除了 α 晶状蛋白对 RGC 的保护功能外，β 和 γ 晶状蛋白还参与 RGC 轴突再生。这些发现表明晶状蛋白基因在 RGC 存活和再生中的重要性，需要进一步深入研究以更好地了解这些蛋白质在健康 RGC 以及在青光眼神经变性中的功能机制，这反过来又有助于设计新的治疗策略来保护或再生这些细胞。
