Elevated Retina-Specific Expression of the Small Heat Shock Protein, αA-crystallin, Is Associated with Photoreceptor Protection in Experimental Uveitis

Rao, Narsing A.; Saraswathy, Sindhu; Wu, Guey-Shuang; Katselis, George; Wawrousek, Eric F.; Bhat, Suraj P.

doi:10.1167/iovs.07-1259

Cited by 78 publications

(95 citation statements)

References 60 publications

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“…Anti-␣A is a polyclonal antibody raised against the N terminus 12 residues (2-13 of the rat ␣A) (16). Anti-␣B is a polyclonal antibody raised against the C terminus, 13 residues (163-175) of the rat ␣B (14, 15).…”

Section: Fractionation Of Homogenates For Enrichment Of Various Membranementioning

confidence: 99%

αA-Crystallin and αB-Crystallin Reside in Separate Subcellular Compartments in the Developing Ocular Lens

Gangalum

Horwitz

Kohan

et al. 2012

Journal of Biological Chemistry

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Background:The small heat shock proteins, ␣A-crystallin and ␣B-crystallin are considered to be two subunits of one single monolithic lens protein, ␣-crystallin. Results: ␣A-Crystallin and ␣B-crystallin fractionate independent of each other and in two separate membrane compartments. Conclusion: ␣A-Crystallin and ␣B-crystallin are two independent proteins in the lens. Significance: These data provide functional insight into why ␣A-crystallin and ␣B-crystallin null mice have disparate phenotypes.

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Section: Fractionation Of Homogenates For Enrichment Of Various Membranementioning

confidence: 99%

αA-Crystallin and αB-Crystallin Reside in Separate Subcellular Compartments in the Developing Ocular Lens

Gangalum

Horwitz

Kohan

et al. 2012

Journal of Biological Chemistry

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“…Oxidative stress leads to up-regulation of a host of Hsp, including α-crystallins (16). Rao et al demonstrated that photoreceptors selectively up-regulated αA-crystallin against immune-mediated mitochondrial oxidative stress by EAU involving the retina (6). We recently demonstrated that mitochondrial oxidative stress occurs in the photoreceptor inner segment in SO globes of humans (11).…”

Section: Discussionmentioning

confidence: 94%

“…On the other hand, in the retina where αA-crystallin immunoreactivity was markedly detected, no TUNEL-positive signals were observed. Rao et al found that αA-crystallin was expressed in the photoreceptors and protected them from apoptotic signals in an EAU model (6). In actuality, αA-crystallin exerts an anti-apoptotic function by blocking pro-apoptotic mitochondrial pathways, thereby inhibiting the activation of downstream apoptotic events (3).…”

Section: Discussionmentioning

confidence: 99%

“…We recently demonstrated that αA-crystallin was up-regulated in the diabetic retina (5), which is possibly correlated with protection of retinal cells from apoptotic signals during progression of diabetic retinopathy. Moreover, a variety of experimental inflammatory models have revealed that up-regulation of αA-or αB-crystallin protected specific cells from apoptotic signals associated with inflammation (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…Induction of Hsp70 leads to amelioration of EAU through suppressed antigen-specific T-cell proliferation (13). Rao et al demonstrated that photoreceptors selectively up-regulated αA-crystallin to protect themselves against immune-mediated mitochondrial oxidative stress in a murine model of EAU (6). These results suggest that Hsp may play an essential role in the suppression of human endogenous uveitis.…”

Section: Introductionmentioning

confidence: 99%

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Expression of α-crystallin in the retina of human sympathetic ophthalmia

et al. 2011

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Abstract. Sympathetic ophthalmia (SO) is a bilateral, granulomatous, intraocular inflammation that occurs following a penetrating injury to one eye, and has the potential to cause blindness of both eyes. The aim of this study was to examine the expression of α-crystallin and to detect apoptotic cells in the retina of human eyes with SO. Five globes, including three with SO and two age-matched normal appearing retinae, were examined. Formalin-fixed, paraffin-embedded tissue sections were submitted to hematoxylin and eosin staining and immunohistochemistry with anti-αA and αB-crystallin antibodies. Apoptotic cells were detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method, and double-staining immunohistochemistry was conducted together with the TUNEL reaction. In normal-appearing retina, αA-crystallin immunoreactivity was predominantly detected in the cytoplasm of photoreceptors, where αB-crystallin was less marked. In SO globes, granulomatous inflammation was noted in the choroid, whereas the retina and choriocapillaris were preserved. Immunoreactivity for αA-crystallin was detected in the retina, as well as in the cytoplasm and inner/ outer photoreceptor segments. By contrast, αB-crystallin was weakly noted in the SO retina. Double-staining immunohistochemistry revealed no TUNEL-positive photoreceptors in the retina displaying high immunoreactivity for αA-crystallin, but photoreceptor apoptosis was noted where expression of αA-crystallin was relatively low. The present study demonstrated that αA-crystallin was up-regulated in the cytoplasm of photoreceptors in the SO retina. This may play a protective role in the suppression of photoreceptor apoptosis associated with intraocular inflammation.

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