A retinal proteomics-based study identifies αA-crystallin as a sex steroid-regulated protein

Sex steroids influence the structural and functional organization of ocular tissues, promote survival in several pathological conditions including retinal neurodegeneration and have a prominent role in age-related eye diseases as well as neurodegenerative diseases. However, their underlying mechanisms are still elusive. We explored proteomic profiling of rat retinas following intravitreal injection of the bioactive 17β-estradiol or androgen dihydrotestosterone. Using narrow range 2-DE gels and MALDI-TOF-MS analysis, we identified three sex steroid-regulated proteins: the galectin-related-inter-fiber (GRIFIN) which is a galectin family member protein of unknown function, the fatty acid-binding protein epidermal-5 (FABP5) protein responsible for the fatty acid uptake and transport and the small heat shock αA-crystallin (CRYAA) protein involved in preventing aggregation of denatured or unfolded proteins. Changes in the expression of these proteins revealed a predominant estrogenic effect and the multiple CRYAA protein species reflected posttranslational modifications. Sex steroid-mediated modifications of CRYAA were confirmed by Western blotting analysis. This study provides new target proteins for sex steroids with a potential link to age-related diseases associated with proteotoxic stress.