Crystallins in Retinal Ganglion Cell Survival and Regeneration

Abstract

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 and thus, be associated with their degeneration. This hypothesis was corroborated by increased survival of axotomized retinal ganglion cells (RGCs) in retinas overexpressing alpha A or alpha B crystallins. In addition to RGC protective functions of alpha crystallins, beta or 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.

A specific phosphorylation regulates the protective role of αA-crystallin in diabetes

“…This pattern of expression is consistent with previous reports in animal models of diabetes (6,26) as well as other neurodegenerative models primarily affecting the inner retina, such as ischemic neuropathies, optic nerve crush, and glaucoma (27). This expression pattern is consistent with studies suggesting a central role for αA-and αB-crystallin in the neuroglial unit in neurodegenerative diseases.…”

Intravitreal injection of β-crystallin B2 improves retinal ganglion cell survival in an experimental animal model of glaucoma

“…As members of the small heat shock protein family, HspB proteins possess of chaperone-like capabilities and incremental expression as a reaction to stress could be observed in different cells and tissues [48, 49]. These findings indicate that crystallins themselves belong directly to the cellular defense mechanism.…”

Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival

“…These crystallin genes were selected since their expression levels were reduced in a OH animal model for glaucoma (Piri et al, 2007; 2013). Regulation of these genes at mRNA and protein levels in response to IOP elevation is described in the following section.…”