Proteasomes in the Cells of the Ocular Surface in Health and Disease

Abstract

PurposeLimbal stem cell deficiency (LSCD) is associated with corneal conjunctivalization that compromises corneal transparency and causes visual impairment. Previously, we found marked changes in proteasome population in corneas of rabbit with LSCD, and showed immunoproteasome (IPR) presence in central corneas during conjunctivalization compared to healthy rabbit cornea. In the present study, we further map the distribution of proteasomes population in the ocular surface.Methodsgene expression intensity obtained by microarray analysis of human healthy corneas and conjunctiva previously reported by the group of Dr. Wolosin (Turner H.C. et al 2007) was used to conduct this study. Constitutive proteasome (CPR) subunits (B5, B2, and B1) were compared to the inducible immunoproteasome (IPR) subunits (B5i, B2i, and B1i). The ratio between CPR and IPR subunits was calculated for cornea and for conjunctiva.ResultsThe comparison of the ratio B5/B5i, B2/B2i and B1/B1i between cornea and conjunctiva showed a significant high expression of CPR in corneas and a high expression of IPR in conjunctivae. In addition, PA28, the regulatory complex of IPR, and the major histocompatibility complex, class I A and B, were found significantly expressed in conjunctiva. Keratins K3/K12 were specifically expressed in cornea and keratins K4/K13 were specifically expressed in conjunctiva, which could be used to normalize the data analysis.ConclusionThe results indicated that conjunctivae contain high levels of IPR and that during conjunctivalization, corneas lose CPR to express IPR. The ration CPR/IPR could be used as an indication of conjunctivalization level in case of corneal injuries.