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The primary cause of obstructive Meibomian gland dysfunction is chronic inflammation (defined as months to years) of the eyes and eyelids

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As noted above, the proteolytic activation step appears to be essential for ligand function, as the introduction of TLD cleavage-resistant mutations into the GDF8 prodomain prevents ligand activation in vitro [76] and in vivo [78] and produces mice with significantly increased muscle mass, similar in phenotype to the phenotype elicited by genetic inactivation of GDF8 or administration of GDF8 inhibitors [78] , despite dramatic elevation of GDF8 levels in the sera of these animals