Analysis of expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human ciliary body after latanoprost.
OBJECTIVE
To determine the effect of latanoprost on the expression of human matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the ciliary body.


METHODS
Total RNA was isolated, and qualitative RT-PCR was performed to detect the mRNA of MMPs and TIMPs in human ciliary body tissue and explant cultures of ciliary body smooth muscle (CBSM) cells. CBSM cell cultures were treated with vehicle control or latanoprost acid for 24 hours. Quantitative RT-PCR of cell cultures from five different donors was performed to determine relative changes in expression. GAPDH served as an endogenous control.


RESULTS
The mRNA of MMP-1, -2, -3, -11, -12, -14, -15, -16, -17, -19, and -24 as well as TIMP-1 to -4 were found in ciliary body tissue and CBSM cells. MMP-9 was present after latanoprost treatment. In control CBSM cells, the relative expression of MMP mRNA was MMP-2 and -14 > MMP-24 > MMP-1, -11, -15, -16, and -19 > MMP-3 and 17, > MMP-12. The relative expression of TIMP mRNA was TIMP-2 > TIMP-1 > TIMP-3 > TIMP-4. Latanoprost increased MMP-3 (in three of five cultures), MMP-17 (in four of five cultures), and TIMP-3 (in all five cultures); MMP-1, -2, -12, -14, -15, and -16 and TIMP-4 were downregulated.


CONCLUSIONS
The transcription of the genes for MMP-3 and -17 is increased by latanoprost treatment. MMP-9 is present after latanoprost treatment and may also mediate ECM changes. TIMP-3 is upregulated and may compensate for the increase in MMPs. These coordinated changes could be expected to mediate the latanoprost-induced alteration of ECM in the ciliary body.
Oh
Dong-Jin
DJ
Laboratory for Molecular Ophthalmology, Wills Eye Hospital, Philadelphia, Pennsylvania, USA.
Martin
Jonathan L
JL
Williams
Adrienne J
AJ
Peck
Rachel E
RE
Pokorny
Corinna
C
Russell
Paul
P
Birk
David E
DE
Rhee
Douglas J
DJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002924:Ciliary Body / Q000187:drug effects* / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D000077338:Latanoprost; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology; D009924:Organ Culture Techniques; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
D000959:Antihypertensive Agents; D011461:Prostaglandins F, Synthetic; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D012313:RNA; D000077338:Latanoprost; D020782:Matrix Metalloproteinases