Elevated levels of proteolytic enzymes in the aging human vitreous.
OBJECTIVE
To identify whether aging of human vitreous is accompanied by an elevation in degradative enzymes within the tissue.


METHODS
Human vitreous samples from donors aged 10 to 88 years were placed in two groups based on donor age of less than or more than 50 years. Homogenized samples were analyzed by gelatin substrate zymography for matrix metalloproteinases (MMP). Serine proteinases were detected by casein substrate zymography, and a specific antibody was used to confirm the identity of, and to quantify, the serine proteinase, plasmin.


RESULTS
Progelatinase A (ProMMP-2) was present in all the vitreous samples but did not show an age-related increase. MMP-2 was also present at low levels. Progelatinase B (ProMMP-9) was found in approximately 80% of samples analyzed, but neither its presence nor level of activity was age dependent. Of the serine proteinase activities detected, an enzyme of approximately 80 kDa was identified by Western blot analysis as plasmin(ogen). Quantitative analysis revealed a significant increase in plasmin(ogen) with age.


CONCLUSIONS
This study shows there is an age-related increase in potential degradative activity in human vitreous that may be responsible for degenerative changes such as vitreous liquefaction. The data suggest that increased levels of these enzymes precede, or are indicative of, underlying ocular disease in some individuals.
Vaughan-Thomas
A
A
Connective Tissue Biology Laboratories, School of Biosciences, Cardiff University, Wales, United Kingdom. vaughan-thomas@cardiff.ac.uk
Gilbert
S J
SJ
Duance
V C
VC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D015153:Blotting, Western; D002648:Child; D004591:Electrophoresis, Polyacrylamide Gel; D004792:Enzyme Precursors / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000378:metabolism*; D014822:Vitreous Body / Q000201:enzymology*
D004792:Enzyme Precursors; D012697:Serine Endopeptidases; D005341:Fibrinolysin; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase