Abstract
Abstract: :
Purpose: To investigate the localization of chondroitin sulfate protoeglycans (CSPG's) in the interphotoreceptor matrix (IPM) of the normal and detached cat retina. Methods: Antibodies were generated to a mixed population of CSPG's that had been treated with chondroitinase prior to injection into mice to ensure that antibodies were not generated against chondroitin sulfate side chains. Antibodies were purified and used for immunohistochemistry and western blotting on normal retinas and those that had been surgically detached for 1,3,7 and 28 days. Results: Individual antibodies recognized multiple bands on western blots suggesting that they recognize multiple CSPG's. Given the limited similarity of the amino acid sequences of CSPG core proteins, it is most likely that these antibodies recognize non-chondroitin sulfate carbohydrate epitopes present on multiple CSPG's. Immunohistochemical staining revealed a wide variety of labeling patterns within the IPM, including the cone matrix, the rod matrix or both. In addition, some of the antibodies yielded staining patterns which revealed compartmentalization of CSPGs specific to the matrix around photoreceptor inner segments while others were specific for the matrix around photoreceptor outer segments. Antibodies made against the core protein of the CSPG aggrecan, for example, only label the matrix sheaths that surround cone outer segments. Following detachment the localization patterns of many CSPG epitopes changed while others did not. Most CSPG epitopes were up-regulated within the IPM following injury, sometimes being expressed in new compartments. One antibody, for example, labeled an epitope that was undetectable in the normal retina yet showed increased expression as detachment time progressed. Conclusion: These data suggest that the IPM contains many different CSPG's that localize to specific, often different compartments. Following experimentally induced injury to the retina, the expression and localization of many of these proteins change, suggesting that CSPG expression is regulated by different mechanisms. Differential regulation of CSPG's after detachment may cause changes in the IPM that contribute to the destabilization and subsequent degeneration of rod and cone photoreceptors.
Keywords: 563 retinal detachment • 529 proteoglycans/glycosaminoglycans • 403 extracellular matrix