Time-Dependent Changes in Muscle IGF1-IGFBP5-PAPP System after Sciatic Denervation.

Denervation-induced muscle atrophy is a frequent cause of skeletal muscle diseases. However, the role of the most important muscle growth factor, insulin-like growth factor (IGF-1), in this process is poorly understood. IGF-1 activity is controlled by six IGF-1 binding proteins (IGFBPs). In skeletal muscle, IGFBP-5 seems to have an important role in atrophic processes. Furthermore, pappalysins (PAPP-A) modulate muscle growth by increasing IGF-1 bioavailability through IGFBP cleavage. We aimed to study the time-dependent changes in the IGF1-IGFBP5-PAPP system and its regulators in gastrocnemius muscle after sciatic denervation. Gastrocnemius atrophy and overexpression of IGF-1 was observed from day 3 post-denervation. The proteolytic factors measured were elevated from day 1 post-denervation onwards. Expression of both IGFBP-5 and pappalysins were increased on days 1 and 3. Subsequently, on days 7 to 14 pappalysins returned to control levels while IGFBP-5 remained elevated. The ratio IGFBP-5/PAPP-A was correlated with the main proteolytic markers. All data suggest that the initial increase of pappalysins could facilitate the IGF-1 action on muscle growth, whereas their subsequent decrease could lead to further muscle wasting.

Long-term changes in corneal morphology induced by overnight orthokeratology.

PURPOSE: To assess long-term morphological and biometric corneal changes produced by overnight orthokeratology and to examine their recovery after cessation of contact lens wear. METHODS: Prospective, single-center, longitudinal trial. Fifteen right eyes with low to moderate myopia underwent overnight orthokeratology for 1 year. The central cornea was examined using a confocal microscope and changes determined in visual acuity, refractive error and corneal topography. Cell counts were performed using both the confocal microscope's software and the image analysis software of the USA Health Institute. All measurements were made during orthokeratology treatment and 1 month after discontinuing treatment. RESULTS: No significant changes in endothelial cell density were observed over time but polymegethism increased significantly and baseline values were not recovered (p < 0.01). Stromal cell density remained unchanged though numbers of activated keratocytes increased during the study and returned to baseline when lens wear ceased. Basal epithelium cell densities significantly fell (p < 0.01) and epithelial wing and superficial cells showed enhanced visibility (p < 0.05). Superficial cells increased in height and width; this width increase being significant after 1 year of orthokeratology (p < 0.01). All epithelial cell changes returned to baseline. Corneal thickness, Bowman layer thickness, subbasal plexus thickness and epithelial thickness were reduced in the central cornea but the stroma was thickened. Of these changes, the decrease in epithelium thickness reached statistical significance (p < 0.01) and baseline values were not recovered. CONCLUSION: Overnight orthokeratology induces structural and optical changes particularly in the central corneal epithelium during myopia treatment. If confirmed, the irreversible changes detected indicate a need for further investigation.