Lacritin and other autophagy associated proteins in ocular surface health

Experimental Eye Research
Roy KarnatiGordon W Laurie

Abstract

Advantage may be taken of macroautophagy ('autophagy') to promote ocular health. Autophagy continually captures aged or damaged cellular material for lysosomal degradation and recyling. When autophagic flux is chronically elevated, or alternatively deficient, health suffers. Chronic elevation of flux and stress are the consequence of inflammatory cytokines or of dry eye tears but not normal tears invitro. Exogenous tear protein lacritin transiently accelerates flux to restore homeostasis invitro and corneal health invivo, and yet the monomeric active form of lacritin appears to be selectively deficient in dry eye. Tissue transglutaminase-dependent cross-linking of monomer decreases monomer quantity and monomer affinity for coreceptor syndecan-1 thereby abrogating activity. Tissue transglutaminase is elevated in dry eye. Mutation of arylsulfatase A, arylsulfatase B, ceroid-lipofuscinosis neuronal 3, mucolipin, or Niemann-Pick disease type C1 respectively underlie several diseases of apparently insufficient autophagic flux that affect the eye, including: metachromatic leukodystrophy, mucopolysaccharidosis type VI, juvenile-onset Batten disease, mucolipidosis IV, and Niemann-Pick type C associated with myelin sheath destruction of...Continue Reading

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Citations

Sep 4, 2020·Translational Vision Science & Technology·Brooke M JustisRobert L McKown
Dec 11, 2019·International Journal of Molecular Sciences·Georgi As GeorgievNorihiko Yokoi
Oct 23, 2020·Ophthalmology and Therapy·Mohamud A VerjeeChristopher E Starr
Feb 2, 2020·American Journal of Ophthalmology·Frederick A JakobiecCarol Shields

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