Crystallins, the major water-soluble proteins of the lens, are also expressed in numerous nonlenticular cell types and tissues, including the brain and the retina.
7,8 Three major classes of proteins make up the crystallins: α-, β-, and γ-crystallins. β-crystallins (βA1/A3, βA2, βA4, βB1, βB2, and βB3) and γ-crystallins (γA-F and γS) are related to microbial proteins induced by physiologic stress,
9 but their exact function, especially in the retina, remain unclear. The two α-crystallins, αA and αB, belong to the small heat shock protein family of molecular chaperones and participate in the regulation of apoptosis. The expression of αA- and αB-crystallins increases after retinal insult, such as light toxicity and retinal trauma, and coincide with increased levels of Bax, caspase-3, and other proteins involved in apoptosis and neurodegeneration.
10,11 αB-crystallin can inhibit stress-induced apoptosis by interacting with proapoptotic members of the Bcl-2 family, Bax and Bcl-Xs, sequestering them in the cytoplasm to prevent them from altering mitochondrial integrity.
12 Overexpression of αA-crystallin in retina during experimental uveitis has a neuroprotective effect on photoreceptor cells, mediated by the interaction of αA-crystallin with cytochrome c and procaspase-3, thereby preventing the activation of the latter.
13 αB-crystallin can confer stress-induced apoptosis resistance to several retinal cell types, including retinal pigment epithelium, pericytes, endothelial cells, and astrocytes.
14 –16