One novel finding in our analysis was the profound upregulation of crystallin-α, -β, and -γ
(Fig. 2) . Traditionally, crystallins have been thought to be lens-rich proteins involved in lens development and maintenance. However, recent studies
10 46 47 48 49 50 suggest that crystallins have broader roles and are expressed beyond lens tissue. Gene-sequence homology studies of crystallins show that members of this family display considerable homology with genes involved in the stress response.
46 47 For instance, the α-crystallins belong to the small heat-shock protein family and may act as molecular chaperones.
46 47 In cultured RPE, αB-crystallin upregulation confers resistance to stress-inducible apoptosis.
48 A recent gene expression study confirmed the increased expression of selected α, β, and γ crystallin transcripts in the rat retina after ischemia-reperfusion injury.
10 Similarly, we found that the mRNA of all 10 crystallins represented in the microarray displayed strong, sustained upregulation after retinal injury. These results are consistent with the increased crystallin protein expression confirmed by Sakaguchi et al.
49 using mass spectrometry after exposing rat retina to light injury. Furthermore, the temporal and spatial expression of crystallins is similar to that of GFAP, implicating this family of proteins in both the local and global response of the retina to trauma. Notably, studies of gene expression in the brain
29 and spinal cord
30 using the identical microarray platform (RG-U34A) did not find a similar upregulation in crystallin-α, -β, and -γ in response to trauma. Whereas crystallin expression in normal mouse retina displays animal-to-animal variation,
50 studies after retinal detachment,
10 light injury,
49 and our retinal tear consistently report the upregulation of crystallins. The coordinated upregulation of crystallins after injury is a potentially important part of the retinal wound-healing process that merits further investigation. Defining the response of the crystallin family to injury illustrates the power of microarray technologies and the discovery-driven approach.